Podcasts about czi

Wednesday, April 9, 2025 – Week 15   Condolences to the Brimsek family and thank you John & Tobi for all your support.  We just shared an interview with our board member and John's son-in-law, Eric Moulton https://cureSYNGAP1.org/Stories    Trip Report, two crazy days.  Many takeaways.  Trials may be coming soon.  If there is a trail, sign up.  Every time. khuba@jcu.edu    Do the Frazier Study and do the follow-ups!  https://curesyngap1.org/eye2 Global as well.  Australia, UK, Canada, please help.   We are busy too!  DiMe announcement just came out https://www.linkedin.com/posts/curesyngap1_new-project-announcement-children-with-activity-7315615778366537728-c-gU    Census is 1,581!  https://curesyngap1.org/blog/syngap1-census-2025-update-q1/   Impact report has a webinar! https://cureSYNGAP1.org/Impact    Both featured in Newsletter #44 - https://cureSYNGAP1.org/NL44   Monday 4/14 we have a webinar - Natural History & Clinical Trial Readiness - with Dr. McKee https://cureSYNGAP1.org/Jill    We have one space available in Colorado on May 20, 2025, email Lauren@curesyngap1.org to sign up.   Other blog about the CB Roadshow, please join us there https://curesyngap1.org/blog/fueling-research-syngap1-combinedbrain-biorepository-roadshow/   And the Polish Community speaking out about ASO trials: https://curesyngap1.org/blog/aso-choice-for-hope-syngap1-voices-from-poland/   #Sprint4Syngap 2025 is in one month! Start or join a team and fundraise! https://curesyngap1.org/sprint25 look at these faces, $66,383 https://www.youtube.com/watch?v=IW7owIsdjss   Bowie - Our funding goes far: https://www.eurekalert.org/news-releases/1078836 remember in July 2022 https://www.eurekalert.org/news-releases/960181    Also see this from CZI, featuring SYNGAP1 in Dr. Willsey's work https://www.czbiohub.org/life-science/unlocking-biology-autism/   PubMed is at 17 YTD, 324 in total (trending to 52+, but I'm not as confident) https://pubmed.ncbi.nlm.nih.gov/?term=syngap1&filter=years.1998-2025&timeline=expanded&sort=date&sort_order=asc   VOLUNTEER  Join us: https://curesyngap1.org/volunteer-with-srf/   SOCIAL MATTERS - 3,996 LinkedIn.  https://www.linkedin.com/company/curesyngap1/ - 1,334 YouTube.  https://www.youtube.com/@CureSYNGAP1  - 11,391 Twitter https://twitter.com/cureSYNGAP1 - 46k Insta https://www.instagram.com/curesyngap1/    NEWLY DIAGNOSED? New families have resources here! https://syngap.fund/Resources    Podcasts, give all of these a five star review! https://podcasts.apple.com/us/channel/syngap1-podcasts-by-srf/id6464522917   Episode 168 of #Syngap10  #Advocate #PatientAdvocacy #UnmetNeed #SYNGAP1 #SynGAP #SynGAProMMiS

“Eventually, my dream would be to simulate a virtual cell.”—Demis HassabisThe aspiration to build the virtual cell is considered to be equivalent to a moonshot for digital biology. Recently, 42 leading life scientists published a paper in Cell on why this is so vital, and how it may ultimately be accomplished. This conversation is with 2 of the authors, Charlotte Bunne, now at EPFL and Steve Quake, a Professor at Stanford University, who heads up science at the Chan-Zuckerberg Initiative The audio (above) is available on iTunes and Spotify. The full video is linked here, at the top, and also can be found on YouTube.TRANSCRIPT WITH LINKS TO AUDIO Eric Topol (00:06):Hello, it's Eric Topol with Ground Truths and we've got a really hot topic today, the virtual cell. And what I think is extraordinarily important futuristic paper that recently appeared in the journal Cell and the first author, Charlotte Bunne from EPFL, previously at Stanford's Computer Science. And Steve Quake, a young friend of mine for many years who heads up the Chan Zuckerberg Initiative (CZI) as well as a professor at Stanford. So welcome, Charlotte and Steve.Steve Quake (00:42):Thanks, Eric. It's great to be here.Charlotte Bunne:Thanks for having me.Eric Topol (00:45):Yeah. So you wrote this article that Charlotte, the first author, and Steve, one of the senior authors, appeared in Cell in December and it just grabbed me, “How to build the virtual cell with artificial intelligence: Priorities and opportunities.” It's the holy grail of biology. We're in this era of digital biology and as you point out in the paper, it's a convergence of what's happening in AI, which is just moving at a velocity that's just so extraordinary and what's happening in biology. So maybe we can start off by, you had some 42 authors that I assume they congregated for a conference or something or how did you get 42 people to agree to the words in this paper?Steve Quake (01:33):We did. We had a meeting at CZI to bring community members together from many different parts of the community, from computer science to bioinformatics, AI experts, biologists who don't trust any of this. We wanted to have some real contrarians in the mix as well and have them have a conversation together about is there an opportunity here? What's the shape of it? What's realistic to expect? And that was sort of the genesis of the article.Eric Topol (02:02):And Charlotte, how did you get to be drafting the paper?Charlotte Bunne (02:09):So I did my postdoc with Aviv Regev at Genentech and Jure Leskovec at CZI and Jure was part of the residency program of CZI. And so, this is how we got involved and you had also prior work with Steve on the universal cell embedding. So this is how everything got started.Eric Topol (02:29):And it's actually amazing because it's a who's who of people who work in life science, AI and digital biology and omics. I mean it's pretty darn impressive. So I thought I'd start off with a quote in the article because it kind of tells a story of where this could go. So the quote was in the paper, “AIVC (artificial intelligence virtual cell) has the potential to revolutionize the scientific process, leading to future breakthroughs in biomedical research, personalized medicine, drug discovery, cell engineering, and programmable biology.” That's a pretty big statement. So maybe we can just kind of toss that around a bit and maybe give it a little more thoughts and color as to what you were positing there.Steve Quake (03:19):Yeah, Charlotte, you want me to take the first shot at that? Okay. So Eric, it is a bold claim and we have a really bold ambition here. We view that over the course of a decade, AI is going to provide the ability to make a transformative computational tool for biology. Right now, cell biology is 90% experimental and 10% computational, roughly speaking. And you've got to do just all kinds of tedious, expensive, challenging lab work to get to the answer. And I don't think AI is going to replace that, but it can invert the ratio. So within 10 years I think we can get to biology being 90% computational and 10% experimental. And the goal of the virtual cell is to build a tool that'll do that.Eric Topol (04:09):And I think a lot of people may not understand why it is considered the holy grail because it is the fundamental unit of life and it's incredibly complex. It's not just all the things happening in the cell with atoms and molecules and organelles and everything inside, but then there's also the interactions the cell to other cells in the outside tissue and world. So I mean it's really quite extraordinary challenge that you've taken on here. And I guess there's some debate, do we have the right foundation? We're going to get into foundation models in a second. A good friend of mine and part of this whole I think process that you got together, Eran Segal from Israel, he said, “We're at this tipping point…All the stars are aligned, and we have all the different components: the data, the compute, the modeling.” And in the paper you describe how we have over the last couple of decades have so many different data sets that are rich that are global initiatives. But then there's also questions. Do we really have the data? I think Bo Wang especially asked about that. Maybe Charlotte, what are your thoughts about data deficiency? There's a lot of data, but do you really have what we need before we bring them all together for this kind of single model that will get us some to the virtual cell?Charlotte Bunne (05:41):So I think, I mean one core idea of building this AIVC is that we basically can leverage all experimental data that is overall collected. So this also goes back to the point Steve just made. So meaning that we basically can integrate across many different studies data because we have AI algorithms or the architectures that power such an AIVC are able to integrate basically data sets on many different scales. So we are going a bit away from this dogma. I'm designing one algorithm from one dataset to this idea of I have an architecture that can take in multiple dataset on multiple scales. So this will help us a bit in being somewhat efficient with the type of experiments that we need to make and the type of experiments we need to conduct. And again, what Steve just said, ultimately, we can very much steer which data sets we need to collect.Charlotte Bunne (06:34):Currently, of course we don't have all the data that is sufficient. I mean in particular, I think most of the tissues we have, they are healthy tissues. We don't have all the disease phenotypes that we would like to measure, having patient data is always a very tricky case. We have mostly non-interventional data, meaning we have very limited understanding of somehow the effect of different perturbations. Perturbations that happen on many different scales in many different environments. So we need to collect a lot here. I think the overall journey that we are going with is that we take the data that we have, we make clever decisions on the data that we will collect in the future, and we have this also self-improving entity that is aware of what it doesn't know. So we need to be able to understand how well can I predict something on this somewhat regime. If I cannot, then we should focus our data collection effort into this. So I think that's not a present state, but this will basically also guide the future collection.Eric Topol (07:41):Speaking of data, one of the things I think that's fascinating is we saw how AlphaFold2 really revolutionized predicting proteins. But remember that was based on this extraordinary resource that had been built, the Protein Data Bank that enabled that. And for the virtual cell there's no such thing as a protein data bank. It's so much more as you emphasize Charlotte, it's so much dynamic and these perturbations that are just all across the board as you emphasize. Now the human cell atlas, which currently some tens of millions, but going into a billion cells, we learned that it used to be 200 cell types. Now I guess it's well over 5,000 and that we have 37 trillion cells approximately in the average person adult's body is a formidable map that's being made now. And I guess the idea that you're advancing is that we used to, and this goes back to a statement you made earlier, Steve, everything we did in science was hypothesis driven. But if we could get computational model of the virtual cell, then we can have AI exploration of the whole field. Is that really the nuts of this?Steve Quake (09:06):Yes. A couple thoughts on that, maybe Theo Karaletsos, our lead AI person at CZI says machine learning is the formalism through which we understand high dimensional data and I think that's a very deep statement. And biological systems are intrinsically very high dimensional. You've got 20,000 genes in the human genome in these cell atlases. You're measuring all of them at the same time in each single cell. And there's a lot of structure in the relationships of their gene expression there that is just not evident to the human eye. And for example, CELL by GENE, our database that collects all the aggregates, all of the single cell transcriptomic data is now over a hundred million cells. And as you mentioned, we're seeing ways to increase that by an order of magnitude in the near future. The project that Jure Leskovec and I worked on together that Charlotte referenced earlier was like a first attempt to build a foundational model on that data to discover some of the correlations and structure that was there.Steve Quake (10:14):And so, with a subset, I think it was the 20 or 30 million cells, we built a large language model and began asking it, what do you understand about the structure of this data? And it kind of discovered lineage relationships without us teaching it. We trained on a matrix of numbers, no biological information there, and it learned a lot about the relationships between cell type and lineage. And that emerged from that high dimensional structure, which was super pleasing to us and really, I mean for me personally gave me the confidence to say this stuff is going to work out. There is a future for the virtual cell. It's not some made up thing. There is real substance there and this is worth investing an enormous amount of CZIs resources in going forward and trying to rally the community around as a project.Eric Topol (11:04):Well yeah, the premise here is that there is a language of life, and you just made a good case that there is if you can predict, if you can query, if you can generate like that. It is reminiscent of the famous Go game of Lee Sedol, that world champion and how the machine came up with a move (Move 37) many, many years ago that no human would've anticipated and I think that's what you're getting at. And the ability for inference and reason now to add to this. So Charlotte, one of the things of course is about, well there's two terms in here that are unfamiliar to many of the listeners or viewers of this podcast, universal representations (UR) and virtual instrument (VIs) that you make a pretty significant part of how you are going about this virtual cell model. So could you describe that and also the embeddings as part of the universal representation (UR) because I think embeddings, or these meaningful relationships are key to what Steve was just talking about.Charlotte Bunne (12:25):Yes. So in order to somewhat leverage very different modalities in order to leverage basically modalities that will take measurements across different scales, like the idea is that we have large, may it be transformer models that might be very different. If I have imaging data, I have a vision transformer, if I have a text data, I have large language models that are designed of course for DNA then they have a very wide context and so on and so forth. But the idea is somewhat that we have models that are connected through the scales of biology because those scales we know. We know which components are somewhat involved or in measurements that are happening upstream. So we have the somewhat interconnection or very large model that will be trained on many different data and we have this internal model representation that somewhat capture everything they've seen. And so, this is what we call those universal representation (UR) that will exist across the scales of biology.Charlotte Bunne (13:22):And what is great about AI, and so I think this is a bit like a history of AI in short is the ability to predict the last years, the ability to generate, we can generate new hypothesis, we can generate modalities that we are missing. We can potentially generate certain cellular state, molecular state have a certain property, but I think what's really coming is this ability to reason. So we see this in those very large language models, the ability to reason about a hypothesis, how we can test it. So this is what those instruments ultimately need to do. So we need to be able to simulate the change of a perturbation on a cellular phenotype. So on the internal representation, the universal representation of a cell state, we need to simulate the fact the mutation has downstream and how this would propagate in our representations upstream. And we need to build many different type of virtual instruments that allow us to basically design and build all those capabilities that ultimately the AI virtual cell needs to possess that will then allow us to reason, to generate hypothesis, to basically predict the next experiment to conduct to predict the outcome of a perturbation experiment to in silico design, cellular states, molecular states, things like that. And this is why we make the separation between internal representation as well as those instruments that operate on those representations.Eric Topol (14:47):Yeah, that's what I really liked is that you basically described the architecture, how you're going to do this. By putting these URs into the VIs, having a decoder and a manipulator and you basically got the idea if you can bring all these different integrations about which of course is pending. Now there are obviously many naysayers here that this is impossible. One of them is this guy, Philip Ball. I don't know if you read the language, How Life Works. Now he's a science journalist and he's a prolific writer. He says, “Comparing life to a machine, a robot, a computer, sells it short. Life is a cascade of processes, each with a distinct integrity and autonomy, the logic of which has no parallel outside the living world.” Is he right? There's no way to model this. It's silly, it's too complex.Steve Quake (15:50):We don't know, alright. And it's great that there's naysayers. If everyone agreed this was doable, would it be worth doing? I mean the whole point is to take risks and get out and do something really challenging in the frontier where you don't know the answer. If we knew that it was doable, I wouldn't be interested in doing it. So I personally am happy that there's not a consensus.Eric Topol (16:16):Well, I mean to capture people's imagination here, if you're successful and you marshal a global effort, I don't know who's going to pay for it because it's a lot of work coming here going forward. But if you can do it, the question here is right today we talk about, oh let's make an organoid so we can figure out how to treat this person's cancer or understand this person's rare disease or whatever. And instead of having to wait weeks for this culture and all the expense and whatnot, you could just do it in a computer and in silico and you have this virtual twin of a person's cells and their tissue and whatnot. So the opportunity here is, I don't know if people get, this is just extraordinary and quick and cheap if you can get there. And it's such a bold initiative idea, who will pay for this do you think?Steve Quake (17:08):Well, CZI is putting an enormous amount of resources into it and it's a major project for us. We have been laying the groundwork for it. We recently put together what I think is if not the largest, one of the largest GPU supercomputer clusters for nonprofit basic science research that came online at the end of last year. And in fact in December we put out an RFA for the scientific community to propose using it to build models. And so we're sharing that resource within the scientific community as I think you appreciate, one of the real challenges in the field has been access to compute resources and industry has it academia at a much lower level. We are able to be somewhere in between, not quite at the level of a private company but the tech company but at a level beyond what most universities are being able to do and we're trying to use that to drive the field forward. We're also planning on launching RFAs we this year to help drive this project forward and funding people globally on that. And we are building a substantial internal effort within CZI to help drive this project forward.Eric Topol (18:17):I think it has the looks of the human genome project, which at time as you know when it was originally launched that people thought, oh, this is impossible. And then look what happened. It got done. And now the sequence of genome is just a commodity, very relatively, very inexpensive compared to what it used to be.Steve Quake (18:36):I think a lot about those parallels. And I will say one thing, Philip Ball, I will concede him the point, the cells are very complicated. The genome project, I mean the sort of genius there was to turn it from a biology problem to a chemistry problem, there is a test tube with a chemical and it work out the structure of that chemical. And if you can do that, the problem is solved. I think what it means to have the virtual cell is much more complex and ambiguous in terms of defining what it's going to do and when you're done. And so, we have our work cut out for us there to try to do that. And that's why a little bit, I established our North Star and CZI for the next decade as understanding the mysteries of the cell and that word mystery is very important to me. I think the molecules, as you pointed out earlier are understood, genome sequenced, protein structure solved or predicted, we know a lot about the molecules. Those are if not solved problems, pretty close to being solved. And the real mystery is how do they work together to create life in the cell? And that's what we're trying to answer with this virtual cell project.Eric Topol (19:43):Yeah, I think another thing that of course is happening concurrently to add the likelihood that you'll be successful is we've never seen the foundation models coming out in life science as they have in recent weeks and months. Never. I mean, I have a paper in Science tomorrow coming out summarizing the progress about not just RNA, DNA, ligands. I mean the whole idea, AlphaFold3, but now Boltz and so many others. It's just amazing how fast the torrent of new foundation models. So Charlotte, what do you think accounts for this? This is unprecedented in life science to see foundation models coming out at this clip on evolution on, I mean you name it, design of every different molecule of life or of course in cells included in that. What do you think is going on here?Charlotte Bunne (20:47):So on the one hand, of course we benefit profits and inherit from all the tremendous efforts that have been made in the last decades on assembling those data sets that are very, very standardized. CELLxGENE is very somehow AI friendly, as you can say, it is somewhat a platform that is easy to feed into algorithms, but at the same time we actually also see really new building mechanisms, design principles of AI algorithms in itself. So I think we have understood that in order to really make progress, build those systems that work well, we need to build AI tools that are designed for biological data. So to give you an easy example, if I use a large language model on text, it's not going to work out of the box for DNA because we have different reading directions, different context lens and many, many, many, many more.Charlotte Bunne (21:40):And if I look at standard computer vision where we can say AI really excels and I'm applying standard computer vision, vision transformers on multiplex images, they're not going to work because normal computer vision architectures, they always expect the same three inputs, RGB, right? In multiplex images, I'm measuring up to 150 proteins potentially in a single experiment, but every study will measure different proteins. So I deal with many different scales like larger scales and I used to attention mechanisms that we have in usual computer vision. Transformers are not going to work anymore, they're not going to scale. And at the same time, I need to be completely flexible in whatever input combination of channel I'm just going to face in this experiment. So this is what we right now did for example, in our very first work, inheriting the design principle that we laid out in the paper AI virtual cell and then come up with new AI architectures that are dealing with these very special requirements that biological data have.Charlotte Bunne (22:46):So we have now a lot of computer scientists that work very, very closely have a very good understanding of biologists. Biologists that are getting much and much more into the computer science. So people who are fluent in both languages somewhat, that are able to now build models that are adopted and designed for biological data. And we don't just take basically computer vision architectures that work well on street scenes and try to apply them on biological data. So it's just a very different way of thinking about it, starting constructing basically specialized architectures, besides of course the tremendous data efforts that have happened in the past.Eric Topol (23:24):Yeah, and we're not even talking about just sequence because we've also got imaging which has gone through a revolution, be able to image subcellular without having to use any types of stains that would disrupt cells. That's another part of the deep learning era that came along. One thing I thought was fascinating in the paper in Cell you wrote, “For instance, the Short Read Archive of biological sequence data holds over 14 petabytes of information, which is 1,000 times larger than the dataset used to train ChatGPT.” I mean that's a lot of tokens, that's a lot of stuff, compute resources. It's almost like you're going to need a DeepSeek type of way to get this. I mean not that DeepSeek as its claim to be so much more economical, but there's a data challenge here in terms of working with that massive amount that is different than the human language. That is our language, wouldn't you say?Steve Quake (24:35):So Eric, that brings to mind one of my favorite quotes from Sydney Brenner who is such a wit. And in 2000 at the sort of early first flush of success in genomics, he said, biology is drowning in a sea of data and starving for knowledge. A very deep statement, right? And that's a little bit what the motivation was for putting the Short Read Archive statistic into the paper there. And again, for me, part of the value of this endeavor of creating a virtual cell is it's a tool to help us translate data into knowledge.Eric Topol (25:14):Yeah, well there's two, I think phenomenal figures in your Cell paper. The first one that kicks across the capabilities of the virtual cell and the second that compares the virtual cell to the real or the physical cell. And we'll link that with this in the transcript. And the other thing we'll link is there's a nice Atlantic article, “A Virtual Cell Is a ‘Holy Grail' of Science. It's Getting Closer.” That might not be quite close as next week or year, but it's getting close and that's good for people who are not well grounded in this because it's much more taken out of the technical realm. This is really exciting. I mean what you're onto here and what's interesting, Steve, since I've known you for so many years earlier in your career you really worked on omics that is being DNA and RNA and in recent times you've made this switch to cells. Is that just because you're trying to anticipate the field or tell us a little bit about your migration.Steve Quake (26:23):Yeah, so a big part of my career has been trying to develop new measurement technologies that'll provide insight into biology. And decades ago that was understanding molecules. Now it's understanding more complex biological things like cells and it was like a natural progression. I mean we built the sequencers, sequenced the genomes, done. And it was clear that people were just going to do that at scale then and create lots of data. Hopefully knowledge would get out of that. But for me as an academic, I never thought I'd be in the position I'm in now was put it that way. I just wanted to keep running a small research group. So I realized I would have to get out of the genome thing and find the next frontier and it became this intersection of microfluidics and genomics, which as you know, I spent a lot of time developing microfluidic tools to analyze cells and try to do single cell biology to understand their heterogeneity. And that through a winding path led me to all these cell atlases and to where we are now.Eric Topol (27:26):Well, we're fortunate for that and also with your work with CZI to help propel that forward and I think it sounds like we're going to need a lot of help to get this thing done. Now Charlotte, as a computer scientist now at EPFL, what are you going to do to keep working on this and what's your career advice for people in computer science who have an interest in digital biology?Charlotte Bunne (27:51):So I work in particular on the prospect of using this to build diagnostic tools and to make diagnostics in the clinic easier because ultimately we have somewhat limited capabilities in the hospital to run deep omics, but the idea of being able to somewhat map with a cheaper and lighter modality or somewhat diagnostic test into something much richer because a model has been seeing all those different data and can basically contextualize it. It's very interesting. We've seen all those pathology foundation models. If I can always run an H&E, but then decide when to run deeper diagnostics to have a better or more accurate prediction, that is very powerful and it's ultimately reducing the costs, but the precision that we have in hospitals. So my faculty position right now is co-located between the School of Life Sciences, School of Computer Science. So I have a dual affiliation and I'm affiliated to the hospitals to actually make this possible and as a career advice, I think don't be shy and stick to your discipline.Charlotte Bunne (28:56):I have a bachelor's in biology, but I never only did biology. I have a PhD in computer science, which you would think a bachelor in biology not necessarily qualifies you through. So I think this interdisciplinarity also requires you to be very fluent, very comfortable in reading many different styles of papers and publications because a publication in a computer science venue will be very, very different from the way we write in biology. So don't stick to your study program, but just be free in selecting whatever course gets you closer to the knowledge you need in order to do the research or whatever task you are building and working on.Eric Topol (29:39):Well, Charlotte, the way you're set up there with this coalescence of life science and computer science is so ideal and so unusual here in the US, so that's fantastic. That's what we need and that's really the underpinning of how you're going to get to the virtual cells, getting these two communities together. And Steve, likewise, you were an engineer and somehow you became one of the pioneers of digital biology way back before it had that term, this interdisciplinary, transdisciplinary. We need so much of that in order for you all to be successful, right?Steve Quake (30:20):Absolutely. I mean there's so much great discovery to be done on the boundary between fields. I trained as a physicist and kind of made my career this boundary between physics and biology and technology development and it's just sort of been a gift that keeps on giving. You've got a new way to measure something, you discover something new scientifically and it just all suggests new things to measure. It's very self-reinforcing.Eric Topol (30:50):Now, a couple of people who you know well have made some pretty big statements about this whole era of digital biology and I think the virtual cell is perhaps the biggest initiative of all the digital biology ongoing efforts, but Jensen Huang wrote, “for the first time in human history, biology has the opportunity to be engineering, not science.” And Demis Hassabis wrote or said, ‘we're seeing engineering science, you have to build the artifact of interest first, and then once you have it, you can use the scientific method to reduce it down and understand its components.' Well here there's a lot to do to understand its components and if we can do that, for example, right now as both of AI drug discoveries and high gear and there's umpteen numbers of companies working on it, but it doesn't account for the cell. I mean it basically is protein, protein ligand interactions. What if we had drug discovery that was cell based? Could you comment about that? Because that doesn't even exist right now.Steve Quake (32:02):Yeah, I mean I can say something first, Charlotte, if you've got thoughts, I'm curious to hear them. So I do think AI approaches are going to be very useful designing molecules. And so, from the perspective of designing new therapeutics, whether they're small molecules or antibodies, yeah, I mean there's a ton of investment in that area that is a near term fruit, perfect thing for venture people to invest in and there's opportunity there. There's been enough proof of principle. However, I do agree with you that if you want to really understand what happens when you drug a target, you're going to want to have some model of the cell and maybe not just the cell, but all the different cell types of the body to understand where toxicity will come from if you have on-target toxicity and whether you get efficacy on the thing you're trying to do.Steve Quake (32:55):And so, we really hope that people will use the virtual cell models we're going to build as part of the drug discovery development process, I agree with you in a little of a blind spot and we think if we make something useful, people will be using it. The other thing I'll say on that point is I'm very enthusiastic about the future of cellular therapies and one of our big bets at CZI has been starting the New York Biohub, which is aimed at really being very ambitious about establishing the engineering and scientific foundations of how to engineer completely, radically more powerful cellular therapies. And the virtual cell is going to help them do that, right? It's going to be essential for them to achieve that mission.Eric Topol (33:39):I think you're pointing out one of the most important things going on in medicine today is how we didn't anticipate that live cell therapy, engineered cells and ideally off the shelf or in vivo, not just having to take them out and work on them outside the body, is a revolution ongoing, and it's not just in cancer, it's in autoimmune diseases and many others. So it's part of the virtual cell need. We need this. One of the things that's a misnomer, I want you both to comment on, we keep talking about single cell, single cell. And there's a paper spatial multi-omics this week, five different single cell scales all integrated. It's great, but we don't get to single cell. We're basically looking at 50 cells, 100 cells. We're not doing single cell because we're not going deep enough. Is that just a matter of time when we actually are doing, and of course the more we do get down to the single or a few cells, the more insights we're going to get. Would you comment about that? Because we have all this literature on single cell comes out every day, but we're not really there yet.Steve Quake (34:53):Charlotte, do you want to take a first pass at that and then I can say something?Charlotte Bunne (34:56):Yes. So it depends. So I think if we look at certain spatial proteomics, we still have subcellular resolutions. So of course, we always measure many different cells, but we are able to somewhat get down to resolution where we can look at certain colocalization of proteins. This also goes back to the point just made before having this very good environment to study drugs. If I want to build a new drug, if I want to build a new protein, the idea of building this multiscale model allows us to actually simulate different, somehow binding changes and binding because we simulate the effect of a drug. Ultimately, the redouts we have they are subcellular. So of course, we often in the spatial biology, we often have a bit like methods that are rather coarse they have a spot that averages over certain some cells like hundreds of cells or few cells.Charlotte Bunne (35:50):But I think we also have more and more technologies that are zooming in that are subcellular where we can actually tag or have those probe-based methods that allow us to zoom in. There's microscopy of individual cells to really capture them in 3D. They are of course not very high throughput yet, but it gives us also an idea of the morphology and how ultimately morphology determine certain somehow cellular properties or cellular phenotype. So I think there's lots of progress also on the experimental and that ultimately will back feed into the AI virtual cell, those models that will be fed by those data. Similarly, looking at dynamics, right, looking at live imaging of individual cells of their morphological changes. Also, this ultimately is data that we'll need to get a better understanding of disease mechanisms, cellular phenotypes functions, perturbation responses.Eric Topol (36:47):Right. Yes, Steve, you can comment on that and the amazing progress that we have made with space and time, spatial temporal resolution, spatial omics over these years, but that we still could go deeper in terms of getting to individual cells, right?Steve Quake (37:06):So, what can we do with a single cell? I'd say we are very mature in our ability to amplify and sequence the genome of a single cell, amplify and sequence the transcriptome of a single cell. You can ask is one cell enough to make a biological conclusion? And maybe I think what you're referring to is people want to see replicates and so you can ask how many cells do you need to see to have confidence in any given biological conclusion, which is a reasonable thing. It's a statistical question in good science. I think I've been very impressed with how the mass spec people have been doing recently. I think they've finally cracked the ability to look at proteins from single cells and they can look at a couple thousand proteins. That was I think one of these Nature method of the year things at the end of last year and deep visual proteomics.Eric Topol (37:59):Deep visual proteomics, yes.Steve Quake (38:00):Yeah, they are over the hump. Yeah, they are over the hump with single cell measurements. Part of what's missing right now I think is the ability to reliably do all of that on the same cell. So this is what Charlotte was referring to be able to do sort of multi-modal measurements on single cells. That's kind of in its infancy and there's a few examples, but there's a lot more work to be done on that. And I think also the fact that these measurements are all destructive right now, and so you're losing the ability to look how the cells evolve over time. You've got to say this time point, I'm going to dissect this thing and look at a state and I don't get to see what happens further down the road. So that's another future I think measurement challenge to be addressed.Eric Topol (38:42):And I think I'm just trying to identify some of the multitude of challenges in this extraordinarily bold initiative because there are no shortage and that's good about it. It is given people lots of work to do to overcome, override some of these challenges. Now before we wrap up, besides the fact that you point out that all the work has to be done and be validated in real experiments, not just live in a virtual AI world, but you also comment about the safety and ethics of this work and assuming you're going to gradually get there and be successful. So could either or both of you comment about that because it's very thoughtful that you're thinking already about that.Steve Quake (41:10):As scientists and members of the larger community, we want to be careful and ensure that we're interacting with people who said policy in a way that ensures that these tools are being used to advance the cause of science and not do things that are detrimental to human health and are used in a way that respects patient privacy. And so, the ethics around how you use all this with respect to individuals is going to be important to be thoughtful about from the beginning. And I also think there's an ethical question around what it means to be publishing papers and you don't want people to be forging papers using data from the virtual cell without being clear about where that came from and pretending that it was a real experiment. So there's issues around those sorts of ethics as well that need to be considered.Eric Topol (42:07):And of those 40 some authors, do you around the world, do you have the sense that you all work together to achieve this goal? Is there kind of a global bonding here that's going to collaborate?Steve Quake (42:23):I think this effort is going to go way beyond those 40 authors. It's going to include a much larger set of people and I'm really excited to see that evolve with time.Eric Topol (42:31):Yeah, no, it's really quite extraordinary how you kick this thing off and the paper is the blueprint for something that we are all going to anticipate that could change a lot of science and medicine. I mean we saw, as you mentioned, Steve, how that deep visual proteomics (DVP) saved lives. It was what I wrote a spatial medicine, no longer spatial biology. And so, the way that this can change the future of medicine, I think a lot of people just have to have a little bit of imagination that once we get there with this AIVC, that there's a lot in store that's really quite exciting. Well, I think this has been an invigorating review of that paper and some of the issues surrounding it. I couldn't be more enthusiastic for your success and ultimately where this could take us. Did I miss anything during the discussion that we should touch on before we wrap up?Steve Quake (43:31):Not from my perspective. It was a pleasure as always Eric, and a fun discussion.Charlotte Bunne (43:38):Thanks so much.Eric Topol (43:39):Well thank you both and all the co-authors of this paper. We're going to be following this with the great interest, and I think for most people listening, they may not know that this is in store for the future. Someday we will get there. I think one of the things to point out right now is the models we have today that large language models based on transformer architecture, they're going to continue to evolve. We're already seeing so much in inference and ability for reasoning to be exploited and not asking for prompts with immediate answers, but waiting for days to get back. A lot more work from a lot more computing resources. But we're going to get models in the future to fold this together. I think that's one of the things that you've touched on the paper so that whatever we have today in concert with what you've laid out, AI is just going to keep getting better.Eric Topol (44:39):The biology that these foundation models are going to get broader and more compelling as to their use cases. So that's why I believe in this. I don't see this as a static situation right now. I just think that you're anticipating the future, and we will have better models to be able to integrate this massive amount of what some people would consider disparate data sources. So thank you both and all your colleagues for writing this paper. I don't know how you got the 42 authors to agree to it all, which is great, and it's just a beginning of something that's a new frontier. So thanks very much.Steve Quake (45:19):Thank you, Eric.**********************************************Thanks for listening, watching or reading Ground Truths. Your subscription is greatly appreciated.If you found this podcast interesting please share it!That makes the work involved in putting these together especially worthwhile.All content on Ground Truths—newsletters, analyses, and podcasts—is free, open-access, with no ads..Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. And such support is becoming more vital In light of current changes of funding by US biomedical research at NIH and other governmental agencies.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research. Get full access to Ground Truths at erictopol.substack.com/subscribe

Nonprofit NewsFeed Podcast: Trump Administration Impact & Philanthropy's Response Episode Summary In this episode of the Nonprofit News Feed Podcast, host Nick Azulay is joined by Whole Whale COO and President Megan Anhalt to discuss the new Trump administration's impact on the social impact sector and philanthropy. The conversation covers the federal funding freeze affecting numerous nonprofit organizations, particularly highlighting the stop work order affecting unaccompanied minors in immigration proceedings and the devastating fallout from USAID funding cuts. As organizations struggle to fill these gaps, they examine the critical role philanthropy must play during this crisis. The hosts then do a deep dive into the Chan Zuckerberg Initiative's (CZI) recent decision to end its social advocacy funding, including work on immigration reform and racial equity, and end its DEI efforts—a move that came shortly after Meta (formerly Facebook) made similar cuts. They analyze this as a case study of how even the most well-resourced philanthropic entities are yielding to political pressure.

Nonprofit NewsFeed Podcast: Trump Administration Impact & Philanthropy's Response Episode Summary In this episode of the Nonprofit News Feed Podcast, host Nick Azulay is joined by Whole Whale COO and President Megan Anhalt to discuss the new Trump administration's impact on the social impact sector and philanthropy. The conversation covers the federal funding freeze affecting numerous nonprofit organizations, particularly highlighting the stop work order affecting unaccompanied minors in immigration proceedings and the devastating fallout from USAID funding cuts. As organizations struggle to fill these gaps, they examine the critical role philanthropy must play during this crisis. The hosts then do a deep dive into the Chan Zuckerberg Initiative's (CZI) recent decision to end its social advocacy funding, including work on immigration reform and racial equity, and end its DEI efforts—a move that came shortly after Meta (formerly Facebook) made similar cuts. They analyze this as a case study of how even the most well-resourced philanthropic entities are yielding to political pressure.

Are you a woman in leadership struggling to manage stress and are not feeling like your authentic self? In this episode of How Women Inspire, Liz Sklar, Director of Stand and Deliver and actress, shares her journey from stage to C-suite and how she helps leaders find their authentic voice and communicate powerfully. Liz and Julie discuss the importance of managing stress, setting boundaries, and embracing your personal values to become a more impactful and authentic leader. They also explore the power of storytelling, emotional resilience, and overcoming self-doubt for women in leadership.In this episode of How Women Inspire Podcast, Liz Sklar is sharing the importance of managing stress and setting boundaries  and actionable steps you can take right now to lead with authenticity and sincerity.In her work with clients including Genentech, Gilead, Twilio, Google, IVP, CZI, Waymo, and the Cartier Women's Initiative, Liz's work has crossed industries from pharma to finance and frequently focuses on leaders in the innovation economy. She is especially inspired by female entrepreneurs and executives and is invested in empowering them to harness their innate power and wisdom to further their careers and expand their missions. Liz has acted professionally in both film and theater, including leading roles at premier regional theaters such as California Shakespeare Festival and American Conservatory Theatre.Some of the talking points Julie and Liz go over in this episode include:How Liz's experience in theatre informs her leadership coaching in the corporate world.Emphasizing the value of finding and showcasing one's authentic self.Managing stress and influencing without authority in the workplace.Encouraging and supporting women leaders through empathy and public speaking.Thank you for listening! If you enjoyed this episode, take a screenshot of the episode to post in your stories and tag me!  And don't forget to follow, rate, and review the podcast and tell me your key takeaways!Learn more about How Women Inspire at https://www.howwomenlead.com/podcast CONNECT WITH LIZ SKLAR:LinkedInWebsiteStand & DeliverCONNECT WITH JULIE CASTRO ABRAMS:LinkedIn - JulieHow Women LeadHow Women InvestHow Women GiveInstagram - HWLLinkedIn - HWLFacebook - HWL

When I think of digital biology, I think of Patrick Hsu—he's the prototype, a rarified talent in both life and computer science, who recently led the team that discovered bridge RNAs, what may be considered CRISPR 3.0 for genome editing, and is building new generative A.I. models for life science. You might call them LLLMs-large language of life models. He is Co-Founder and a Core Investigator of the Arc Institute and Assistant Professor of Bioengineering and Deb Faculty Fellow at the University of California, Berkeley.Above is a brief snippet of our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Here's the transcript with links to the audio and external links to relevant papers and things we discussed.Eric Topol (00:06):Well hello, it's Eric Topol with Ground Truths and I'm really delighted to have with me today Patrick Hsu. Patrick is a co-founder and core investigator at the Arc Institute and he is also on the faculty at the University of California Berkeley. And he has been lighting things up in the world of genome editing and AI and we have a lot to talk about. So welcome, Patrick.Patrick Hsu (00:29):Thanks so much. I'm looking forward to it. Appreciate you having me on, Eric.The Arc InstituteEric Topol (00:33):Well, the first thing I'd like to get into, because you're into so many important things, but one that stands out of course is this Arc Institute with Patrick Collison who I guess if you can tell us a bit about how you two young guys got to meet and developed something that's really quite unique that I think brings together investigators at Stanford, UCSF, and Berkeley. Is that right? So maybe you can give us the skinny about you and Patrick and how all this got going.Patrick Hsu (01:05):Yeah, sure. That sounds great. So we started Arc with Patrick C and with Silvana Konermann, a longtime colleague and chemistry faculty at Stanford about three years ago now, though we've been physically operational just over two years and we're an independent research institute working at the interface of biomedical science and machine learning. And we have a few different aspects of our model, but our overall mission is to understand and treat complex human diseases. And we have three pillars to our model. We have this PI driven side of the house where we centrally fund our investigators so that they don't have to write grants and work on their very best ideas. We have a technical staff side of the house more like you'd see in a frontier AI lab or in biotech industry where we have professional teams of R&D scientists working cross-functionally on higher level organizational wide goals that we call our institute initiatives.(02:05):One focused on Alzheimer's disease experimentally and one that we call a virtual cell initiative to simulate human biology with AI foundation models. And our third pillar over time is to have things not just end up as academic papers, but really get things out into the real world as products or as medicines that can actually help patients on the translational side. And so, we thought that some really important scientific programs could be unlocked by enabling new organizational models and we are experimenting at the institutional scale with how we can better organize and incentivize and support scientists to reach these long-term capability breakthroughs.Patrick, Patrick and SilvanaEric Topol (02:52):So the two Patrick's. How did you, one Patrick I guess is a multi-billionaire from Stripe and then there's you who I suspect maybe not quite as wealthy as the other Patrick, how did you guys come together to do this extraordinary thing?Patrick Hsu (03:08):Yeah, no, science is certainly expensive. I met Patrick originally through Silvana actually. They actually met, so funny trivia, all three Arc founders did high school science together. Patrick and Silvana originally met in the European version of the European Young Scientist competition in high school. And Silvana and I met during our PhDs in her case at MIT and I was at Harvard, but we met at the Broad Institute sort of also a collaborative Harvard, MIT and Harvard hospitals Institute based in Kendall Square. And so, we sort of in various pairwise combinations known each other for decades and worked together for decades and have all collectively been really excited about science and technology and its potential to accelerate societal progress. Yet we also felt in our own ways that despite a lot of the tremendous progress, the structures in which we do this work, fund it, incentivize it and roll it out into the real world, seems like it's really possible that we'll undershoot that potential. And if you take 15 years ago, we didn't have the modern transformer that launched the current AI revolution, CRISPR technology, single-cell, mRNA technology or broadly addressable LNPs. That's a tremendous amount of technologies have developed in the next 15 years. We think there's a real unique opportunity for new institutes in the 2020s to take advantage of all of these breakthroughs and the new ones that are coming to continue to accelerate biological progress but do so in a way that's fast and flexible and really focused.Eric Topol (04:58):Yeah, I did want to talk with you a bit. First of all before I get to the next related topic, I get a kick out of you saying you've worked or known each other for decades because I think you're only in your early thirties. Is that right?Patrick Hsu (05:14):I was lucky to get an early start. I first started doing research at the local university when I was 14 actually, and I was homeschooled actually until college. And so, one of the funny things that you got to do when you're homeschooled is well, you could do whatever you want. And in my case that was work in the lab. And so, I actually worked basically full time as an intern volunteer, cut my teeth in single cell patch clamp, molecular biology, protein biochemistry, two photon and focal imaging and kind of spiraled from there. I loved the lab, I loved doing bench work. It was much more exciting to me than programming computers, which was what I was doing at the time. And I think these sort of two loves have kind of brought me and us to where we are today.Eric Topol (06:07):Before you got to Berkeley and Arc, I know you were at Broad Institute, but did you also pick up formal training in computer science and AI or is that something that was just part of the flow?Patrick Hsu (06:24):So I grew up coding. I used to work through problems sets before dinner growing up. And so, it's just something that you kind of learn natively just like learning French or Mandarin.New Models of Funding Life ScienceEric Topol (06:42):That's what I figured. Okay. Now this model of Arc Institute came along in a kind of similar timeframe as the Arena BioWorks in Boston, where some of the faculty left to go to Arena like my friend Stuart Schreiber and many others. And then of course Priscilla and Mark formed the Chan Zuckerberg Institute and its biohub and its support. So can you contrast for one, these three different models because they're both very different than of course the traditional NIH pathway, how Arc is similar or different to the others, and obviously the goal here is accelerating things that are going to really make a difference.Patrick Hsu (07:26):Yeah, the first thing I would say is zooming out. There have been lots of efforts to experiment with how we do science, the practice of science itself. And in fact, I've recently been reading this book, the Demon Under the Microscope about the history of infectious disease, and it talks about how in the 1910s through the 1930s, these German industrial dye manufacturing companies like Bayer and BASF actually launched what became essentially an early model for industrial scale science, where they were trying to develop Prontosil, Salvarsan and some of these early anti-infectives that targeted streptococcus. And these were some of the major breakthroughs that led to huge medical advances on tackling infectious disease compared to the more academic university bound model. So these trends of industrial versus academic labs and different structures to optimize breakthroughs and applications has been a through current throughout international science for the last century.(08:38):And so, the way that we do research today, and that's some of our core tenets at Arc is basically it hasn't always been this way. It doesn't need to necessarily be this way. And so, I think organizational experiments should really matter. And so, there's CZI, Altos, Arena, Calico, a variety of other organizational experiments and similarly we had MRC and Bell Labs and Xerox PARCS, NIBRT, GNF, Google Research, and so on. And so, I think there are lots of different ways that you can organize folks. I think at a high level you can think about ways that you can play with for-profit versus nonprofit structures. Whether you want to be a completely independent organization or if you want to be partnered with universities. If you want to be doing application driven science or really blue sky curiosity driven work. And I think also thinking through internally the types of expertise that you bring together.(09:42):You can think of it like a cancer institute maybe as a very vertically integrated model. You have folks working on all kinds of different areas surrounding oncology or immunotherapy and you might call that the Tower of Babel model. The other way that folks have built institutes, you might call the lily pad model where you have coverage of as many areas of biomedical research as possible. Places like the Whitehead or Salk, it will be very broad. You'll have planned epigenetics, folks looking at RNA structural biology, people studying yeast cell cycle, folks doing in vivo melanoma models. It's very broad and I think what we try to do at Arc is think about a model that you might liken more to overlapping Viking shields where there's sort of five core areas that we're deeply investing in, in genetics and genomics, computation, neuroscience, immunology and chemical biology. Now we really think of these as five areas that are maybe the minimal critical mass that you would need to make a dent on something as complicated as complex human diseases. It's certainly not the only thing that you need, but we needed a critical mass of investigators working at least in these areas.Eric Topol (11:05):Well, yeah, and they really converge on where the hottest advances are being made these days. Now can you work at Arc Institute without being one of these three universities or is it really that you maintain your faculty and your part of this other entity?Patrick Hsu (11:24):So we have a few elements to even just the academic side of the house. We have our core investigators. I'm one of them, where we have dually appointed faculty who retain their latter rank or tenured appointment in their home department, but their labs are physically cited at the Arc headquarters where we built out a lab in Stanford Research Park in Palo Alto. And so, folks move their labs there. They continue to train graduate students based on whatever graduate programs they're formally affiliated with through their university affiliation. And so, we have nearly 40 PhD students across our labs that are training on site every day.(12:03):So in addition to our core investigators, we also have what we call our innovation investigators, which is more of a grant program to faculty at our partner universities. They receive unrestricted funding from us to seed a new project or accelerate an existing area in their group and their labs stay at their home campus and they just get that funding to augment their work. The third way is our technical staff model where folks basically just come work at Arc and many of them also are establishing their own research groups focusing on technology R&D areas. And so, we have five of those technology centers working in molecular engineering, multi-omics, complex cellular models, in vivo models, and in machine learning.Discovery of Bridge RNAsEric Topol (12:54):Yeah, that's a great structure. In fact, just a few months ago, Patrick Collison, the other Patrick came to Stanford HAI where I'm on the board and you've summarized it really well and it's very different than the other models and other entities, companies included that you mentioned. It's really very impressive. Now speaking of impressive on June 26, this past few months ago, which incidentally is coincident with the draft genome in the year 2000, the human sequence. You and your colleagues, perhaps the most impressive jump in terms of an Arc Institute contribution published two papers back-to-back in Nature about bridge RNA: [Bridge RNAs direct programmable recombination of target and donor DNA] and [Structural mechanism of bridge RNA-guided recombination.] And before I get you to describe this breakthrough in genome editing, some would call it genome editing 3.0 or CRISPR 3.0, whatever. But what we have today in the clinic with the approval of CRISPR 1.0 for sickle cell and thalassemia is actually quite crude. I think most people will know it's just a double stranded DNA cleavage with all sorts of issues about repair and it's not very precise. And so, CRISPR 2.0 is supposed to be represented by David Liu's contributions and his efforts at Broad like prime and base editing and then comes yours. So maybe you can tell us about it and how it is has to be viewed as quite an important advance.Patrick Hsu (14:39):The first thing I would say before CRISPR, is that we had RNA interference. And so, even before this modern genome editing revolution with programmable CRISPRs, we had this technology that had a lot of the core selling points as well. Any target will now become druggable to us. We simply need to reprogram a guide RNA and we can get genetic access to things that are intracellular. And I think both the discovery of RNA interference by Craig Mello and Andy Fire or the invention or discovery of programmable CRISPR technologies, both depend on the same fundamental biological mechanism. These non-coding guide RNAs that are essentially a short RNA search string that you can easily reprogram to retarget a desired enzyme function, and natively both RNAi and CRISPR are molecular scissors. Their RNA or DNA nucleases that can be reprogrammed to different regions of the genome or the transcriptome to make a cut.(15:48):And as bioengineers, we have come up with all kinds of creative ways to leverage the ability to make site specific cuts to do all kinds of incredible things including genome editing or beyond transcriptional up or down regulation, molecular imaging and so on and so forth. And so, the first thing that we started thinking about in our lab was, why would mother nature have stopped only RNAi and CRISPR? There probably are lots of other non-coding RNAs out there that might be able to be programmable and if they did exist, they probably also do more complicated and interesting things than just guide a molecular scissors. So that was sort of the first core kind of intuition that we had. The second intuition that we had on the technology side, I was just wearing my biology hat, I'll put on my technology hat, is the thing that we call genome editing today hardly involves the genome.(16:50):It's really you're making a cut to change an individual base or an individual gene or locus. So really you're doing small scale single locus editing, so you might call it gene level or locus level cuts. And what you really want to be able to do is do things at the genome scale at 100 kb, a megabase at the chromosome scale. And I think that's where I think the field will inevitably go if you follow the technology curves of longer and longer range gene sequencing, longer and longer range gene synthesis, and then longer and longer range gene editing. And so, what would that look like? And we started thinking, could there be essentially recombination technologies that allow you to do cut and paste in a single step. Now, the reason for that is the way that we do gene editing today involves a cut and then a multi-step process of cellular DNA repair that resolves the cut to make the exertion or the error prone deletion or the modification that ends up happening.(17:59):And so, it's very complicated and whether that's nucleases or base or prime editing, you're all generally limited to the small-scale single locus changes. However, there are natural mechanisms that have solved this cut and paste problem, right? There are these viruses or bacterial versions of viruses known as phage that have generally been trying to exert their multi kilobase genomes into bacterial hosts and specialize throughout billions of years. So our core thought was, well, if there are these new non-coding RNAs, what kind of functions would we be excited about? Can we look in these mobile genetic elements, these so-called jumping genes for new mechanisms? They're incredibly widespread. Transposons are thought to be some of the most diverse enzyme mechanisms found in nature. And so, we started computationally by asking ourselves a very simple question. If a mobile element inserts itself into foreign DNA and it's able to somehow be programmable, presumably the inside or something encoded in the inside of the element is predictive of some sequence on the outside of the element.(19:15):And so, that was the core insight we took, and we thought let's look across the boundaries of many different mobile genetic elements and we zoomed in on a particular sub family of these MGE known as insertion sequence (IS) elements which are the most autonomous minimal transposons. Normally transposons have all kinds of genes that they use to hitchhike around the genomic galaxy and endow the bacterial host with some fitness advantage like some ability to metabolize some copper and some host or some metal. And these IS elements have only the enzymes that they need to jump around. And if you identify the boundaries of these using modern computational methods, this is actually a really non-trivial problem. But if you solve that problem to figure out with nucleotide resolution where the element boundaries end and then you look for the open reading frame of the transposases enzyme inside of this element, you'll find that it's not just that coding sequence.(20:19):There are also these non-coding flanks inside of the element boundaries. And when we looked across the non-coding, the entire IS family tree, there are hundreds of these different types of elements. We found that this particular family IS110, had the longest non-coding ends of all IS elements. And we started doing experiments in the lab to try to figure out how these work. And what we found was that these elements are cut and paste elements, so they excise themselves into a circular form and paste themselves back in into a target site linearly. But the circularization of this element brings together two distal ends together, which brings together a -35 and a -10 box that create and reconstitute a canonical bacterial transcriptional promoter. This essentially is like plugging a plug into an electrical socket in the wall and it jacks up transcription. Now you would think this transcription would turn on the transposase enzyme so it can jump around more but it transcribes a non-coding RNA out of this non-coding end.(21:30):We're like, holy crap, are these RNAs actually involved in regulating the transposon? Now the boring answer would be, oh, it regulates the expression. It's like an antisense regulate or something. The exciting answer would be, oh, it's a new type of guide RNA and you found an RNA guided integrase. So we started zooming in bound dramatically on this and we undertook a covariation analysis where we were able to show that this cryptic non-coding RNA has a totally novel guide RNA structure, totally distinct from RNAi or CRISPR guide RNAs. And it had a target site that covaried with the target site of the element. And so we're like, oh wow, this could be a programmable transposase. The second thing that we found was even more surprising, there was a second region of complementarity in that same RNA that recognized the donor sequence, which is the circularized element itself. And so, this was the first example of a bispecific guide RNA, and also the first example of RNA guided self-recognition by a mobile genetic element.Eric Topol (22:39):It's pretty extraordinary because basically you did a systematic assessment of jumping genes or transposons and you found that they contain things that previously were not at all recognized. And then you have a way to program these to edit, change the genome without having to do any cuts or nicks, right?Patrick Hsu (23:05):Yeah. So what we showed in a test tube is when we took this, so-called bridge RNA, which we named because it bridges the target and donor together along with the recombinase enzyme. So the two component system, those are the only two things that you need. They're able to cut and paste DNA and recombine them in a test tube without any DNA repair, meaning that it's independent of cellular DNA repair and it does strand nicking, exchange, junction resolution and religation all in a single mechanism. So that's when we got super excited about its potential applications as bioengineering tool.Eric Topol (23:46):Yeah, it's pretty extraordinary. And have you already gone into in vivo assessment?Patrick Hsu (23:54):Yes, in our initial set of papers, what we showed is that these are programmable and functional or recombinases in a test tube and in bacterial cells. And by reprogramming the target and donor the right way, you can use these enzymes not just for insertion, but also for flipping and cutting out DNA. And so, we actually have in a single mechanism the ability to do bridge editing, if you will, for universal DNA recombination, insertion, excision or inversion, similar to what folks have been doing for decades with Cre recombinase, but with fully programmable recognition sequences. The work that we're doing now in the lab as you can imagine is to adapt these into robust tools for mammalian genome editing, including of course, human genomes. We're excited about this, we're making good progress. The CRISPR has had thousands of labs over the last 10, 15 years working on it to make these therapeutic level potency and selectivity. We're going to work and follow that same blueprint for getting bridge systems to get to that level of performance, but we're on the path and we're very optimistic for the future.Exemplar of Digital BiologyEric Topol (25:13):Yeah, I think it's quite extraordinary and it's a whole different look to what we've been seeing in the CRISPR era for over the past decade and how that's been advancing and getting more specific and less need for repair and being able to be more versatile. But this takes it to yet another dimension. Now, this brings me to the field that when I think of this term digital biology, I think of you and now our mutual acquaintance, Jensen Huang, who everybody knows now. Back some months ago, he wrote and said at a conference, “Where do I think the next amazing revolution is going to come? And this is going to be flat out one of the biggest ones ever. There's no question that digital biology is going to be it. For the first time in human history, biology has the opportunity to be engineering, not science.” So can you critique Jensen? Is he right? And tell us how you conceive the field of digital biology.Patrick Hsu (26:20):If you look at gene therapy today, the core concepts are actually remarkably simple. They're elegant. Of course, you're missing a broken gene, you need to put it back. And that can be curative. Very simple, powerful concept. However, for complex diseases where you don't have just a single gene that goes wrong, in many cases we actually have no idea what to do. And in fact, when you're trying to put in DNA, that's over more than a gene scale. We kind of very quickly run out of ideas. Is it a CAR and a cytokine, a CAR and a cytokine and another thing? And then we're kind of out of ideas. And so, we started thinking in the lab, how can we actually design genomes where it's not just let's reduce the genome into individual Lego blocks, iGem style with promoters and different genes that we just sort of shuffle the Lego blocks around, but actually use AI to design genome sequences.(27:29):So to do that, we thought we would have to first of all, train a model that can learn and decode the foreign language of biology and use that in order to design sequences. And so, we sort of have been training DNA foundation models and virtual cell models at Arc, sort of a major effort of ours where the first thing that we tried was to take a variance of transformer architecture that's used to train ChatGPT from OpenAI, but instead apply this to study the next DNA token, right? Now, the interesting thing about next token prediction in English is that you can actually learn a surprising amount of information by just predicting the next word. You can learn world knowledge is the capital of Azerbaijan, is it Baku or is it London, right? Or if you're walking around in the kitchen, then the next text is, I then left the kitchen or the bathroom, right?(28:33):Now you're learning about spatial reasoning, and so you can also learn translation obviously. And so similarly, I think predicting the next token or the next base and DNA can lead you to learn about molecular biochemistry, is the next amino acid residue, hydrophobic or hydrophilic. And it can teach you about the mechanics of some catalytic binding pocket or something. You can learn about a disease mutation. Is the next base, the sick linked base or the wild type base and so on and so forth. And what we found was that at massive scale, DNA foundation models learn about molecular function, not just at the DNA level, but also at the RNA and the protein. And indeed, we could use these to design molecular systems like CRISPR-Cas systems, where you have a protein and the guide RNA. It could also design new DNA transposons, and we could design sequences that look plausibly like real genomes, where we generate a megabase a million bases of continuous genome sequence. And it really looks and feels like it could be a blurry picture of something that you would actually sequence. This has been a wonderful collaboration with Brian Hie, a PI at Stanford and an Arc investigator, and we're really excited about what we've seen in this work because it promises the better performance with even more scale. And so, simply by scaling up these models, by adding in more compute, more training data or more powerful models, they're going to get sharper and sharper.New A.I. Models in Life ScienceEric Topol (30:25):Yeah. Well, this whole use of large language models for the language of life, whether it's the genome proteins and on and on, actually RNA and even cells has really taken root. And of course, this is really one of the foundations of that field of digital biology, which brings together generative AI, AI tools and trying to push forward our understanding in biology. And also, obviously what's been emphasized in drug discovery, perhaps it's been emphasized even too much because we still have a lot to learn about biology, but that gets me to these models. Like today, AlphaProteo was announced by DeepMind, as we all know, AlphaFold 1, 2, now 3. They were kind of precursors of being able to predict proteins from amino acid 3D structure. And that kind of took the field by a little bit like ChatGPT for life science, but now it's a new model all the time. So you've been working on various models and Arc Institute, how do you see this unfolding? Are we just going to have every aspect of the language of life being approached in all the different interactions? And this is going to help us get to a much more deep level of understanding.Patrick Hsu (31:56):I'll say two things. The first is a lot of models that you just described are what I would call task specific models. A model for de novo design of a binder, a model for protein structure prediction. And there are other models for protein fitness or for RNA structure prediction, et cetera, et cetera. And I think what we're going to move towards are more unifying models where there's different classes of models at different levels of scale. So we will have these atomic level models for looking at generative chemistry or ligand docking. We have models that can unify genomes and their molecules, and then we have models that can unify cells and tissues. And so, for example, if you took an H&E stain of some liver, there are folks building models where you can then predict what the single cell spatial transcriptome will look like of that model. And that's obviously operating at a very different level of abstraction than a de novo protein binder. But in the long run, all of these are going to get, I think unified. I think the reason why this is possible is that biology, unlike physics, actually has this unifying theory of evolution that runs across all of its length scales from atomic, molecular, cellular, organismal to entire ecosystem. And the promise of these models is no short then to make biology a predictive discipline.Patrick Hsu (33:37):In physics, the experimentalists win the big prizes for the theorists when they measure gravitational waves or whatever. But in biology, we're very practical people. You do something three times and do a T-test. And I think my prediction is we can actually gauge the success of these LLMs or whatever in biology by how much we respect theory in this field.The A.I. ScientistEric Topol (34:05):Yeah. Well, that's a really interesting perspective, an important perspective because the proliferation of models, which we're going to get into not just doing the things that you described, but also being able to be “pseudo” scientists, the so-called AI scientist. Maybe you could comment about that concept because that's been the idea that everything from the question that could be asked to the hypothesis and the experiment design and the analysis of data and then the feedback. So what is the role of the scientists, that seems to have been overplayed? And maybe you can put that in context.Patrick Hsu (34:48):So yeah, right now there's a lot of excitement that we can use AI agents not just to do software enterprise workflows, but to be a research assistant. And then over time, itself an autonomous research scientist that can read the literature, come up with an idea, maybe run a bunch of robots in the lab or do a bunch of computational analyses and then potentially even analyze data, conclude what is going on and actually write an entire paper. Now, I think the vision of this is compelling in the long term. I think the question is really about timescale. If you break down the scientific method into its constituent parts, like hypothesis generation, doing an experiment, analyzing experiment and iterating, we're clearly going to use AI of some kind at every single step of this cycle. I think different steps will require different levels of maturity. The way that I would liken this is just wet lab automation, folks have dreamed about having pipetting robots that just do their western blots and do their cell culture for them for generations.(36:01):But of course, today they don't actually really feel fundamentally different from the same ones that we had in the 90s, let's say. Right? And so, obviously they're getting better, but it seems to me one of the trends I'm very bullish about is the explosion of humanoid robots and robot foundation models that have a world model and a sense of physics and proportionate space loaded onto them. Within five years, we're going to have home robots that can fold your clothes, that can organize your kitchen and do all of this while you're sleeping, so you wake up to a clean home every day.Eric Topol (36:40):It's not going to be just Roomba anymore. There's going to be a lot more, but it isn't just the hardware, it's also the agents playing in software, right?Patrick Hsu (36:50):It's the integrated loop of the hardware and the software where the ability to make the same machine generally intelligent will make it adaptable to a broad array of tasks. Now, what I'm excited about is those generally intelligent humanoid robots coming into the lab, where instead of creating a centrifuge or a new type of pipetter that's optimized for your Beckman or Hamilton device, instead you just have robot arms that you snap onto the edge of the bench and then they just work alongside you. And I do think that's coming, although it'll take a lot of hardware and software and computer vision engineering to make that possible.A Sense of HumorEric Topol (37:32):Yeah, and I think also going back to originating the question, there still is quite a debate about the creativity and the lack of any simulation of AGI, whatever that means anymore. And so, the human in the loop part of this is obviously I think it's still of critical nature. Now, the other thing I learned about you is you have a great sense of humor, which is really important by the way. And recently, which is great that you're active on X or Twitter because that's one way we get to see what you're thinking on a day-to-day basis. But I think you put out a poll which was really quite provocative , and it was about, here's what it said, “do more people in the world *truly* understand transformers or health insurance?” And interestingly, you got 49% for transformers at 51% for health insurance. Can you tell us what you're thinking when you put that poll together? Because obviously a lot of people don't understand either of these.Patrick Hsu (38:44):I think the core question is, there are different ways of looking at the world, some of which are very bottom up and some of which are very top down. And one of the very surprising things about transformers is they're taking something that is in principle, an incredibly simple task, which is if you have a string of text, what is the next letter? And somehow at massive, massive scale, you can unlock something that looks an awful lot like reasoning, and you've got these emergent behaviors. Now the bottoms up theory of just the linear algebra that's going on in these models couldn't possibly really help us predict that we have these emerging capabilities. And I think similarly in healthcare, there's a literal set of parts that are operating in some complex way that at massive scale becomes this incredibly confusing and dynamic system for how we can actually incentivize how we make medicines, how we actually take care of people, and how we actually pay for any of this from an economic point of view. And so, I think it was, in some sense if transformers can actually be an explainable by just linear algebra equations, maybe there will be a way to decompose the seemingly incredibly confusing world of healthcare in order to actually build a better way forward.Computing Power and the GPU Arms RaceEric Topol (40:12):Yeah. Well that's great. Now the other thing I wanted to ask you about, we open source and the arms race of GPUs and this whole kind of idea is you touched on the need for coalescing a lot of these tools to exploit the synergy. But we have an issue because many academic labs like here at Scripps Research and so many others, including as I learned even at Stanford, have limited access to GPUs. So computing power of large language models is a problem. And then the models that exist today that can be adopted like Llama or others, and they're somewhat limited. And then we also have a movement towards trying to make things more open source, like for example, recently OpenCRISPR with Profluent Bio that is basically trying to use AI for CRISPR guides. And so, how do you deal with this arms race, computing power, open source, proprietary models that are not easily accessible without a lot of resources?Patrick Hsu (41:30):So the first thing I would say is, we are in the academic science sphere really unprepared for the level of resources that are required for doing this type of cutting edge computational work. There are top Stanford computer science professors or computational researchers who have a single GPU in their office, and that's actually what their whole lab runs off of.(41:58):The UC Berkeley campus, the grid runs on something like 12 megawatts of power and how are they going to build an on-premises GPU clusters, like a central question that can scale across the entire needs? And these are two of the top computer science universities in the world. And so, I think one of our kind of core beliefs at Arc is, as science both experimentally and computationally has gotten incredibly complex, not just in terms of conceptually, but also just the actual infrastructure and machines and know-how that you need to do things. We actually need to essentially support this. So we have a private GPU cloud that we use to train our models, and we have access to significantly large clusters for large burst kind of train outs as necessary. And I think infrastructurally for running genomics experiments or doing scalable brain organoid screens, right, we're also building out the infrastructure to support that experimentally.Eric Topol (43:01):Yeah, no, I think this is one of the advantages of the new model like the Arc Institute because not many centers have that type of plasticity with access to computing power when needed. So that's where a brilliant mind you and the Arc Institute together makes for a formidable recipe for future advances and of course building on the ones you've already accomplished.The Primacy of Human TalentPatrick Hsu (43:35):I would just say, my main skill, if I have one, is to recruit really, really smart people. And so, everything that you're seeing and hearing about is the work of unbelievable colleagues who are curious, passionate, and incredible scientists.Eric Topol (43:53):But it also takes the person who can judge those who are in that category set as a role model. And you're certainly doing that. I guess just in closing, I mean, it's just such a delight to get to meet you here and kind of get your thoughts on what is the hottest thing in life science without question, which brings together the fields of AI and what's going on, not just obviously in genome editing, but this digital biology era that we're still in the early phases of, I mean, I think you could say that it's just going to continue to accelerate the exponential curve. We're still kind of on the bottom of that, I would imagine where we're headed. Any other things that you want to bring up that I haven't touched on that will round out this conversation?Patrick Hsu (44:50):I mean, I think it's very early days here at Arc.Patrick Hsu (44:53):When we founded Arc, we asked ourselves, how do we measure success? We don't have customers or revenue in the way that a typical startup does. And we felt sort of three things. The first was research institutes live and die by their talent. Can we actually hire incredible people when we make offers to people we want to come, do they come? The second was, when those folks do come to Arc, do they feel like they're able to work on important research programs that they couldn't do sort of at their prior university or company? And then longer term, the third thing was, and there's just no shortcut around this, you need to do important work. And I think we've been really excited that there are early signs that we're able to do all three of these things, and we're still, again, just following the same scaling laws that we're seeing in natural language and vision, but for the domain of biology. And so, we're excited about what's ahead and think if there are folks who are interested in learning more about Arc, just shoot me an email or DM.Eric Topol (46:07):Yeah, well I would just say, congratulations on what you've already achieved. I know you're going to keep rocking it because you already have in a short time. And for anybody who doesn't know about Arc Institute and your work and your team, I hope this is going to be putting them on notice actually what can be accomplished outside of the usual NIH funded model, which is kind of a risk-free zone where you basically have to have your results nailed down before you send in your proposal frequently, and it doesn't do great things for young people. Really, I think you actually qualify in that demographic where it's hard for them to break in for getting NIH grants and also for this type of work that you're doing. So we'll look for the next bridge beyond bridge RNAs of your just fantastic efforts. So Patrick, thanks so much for joining us today, and we'll be checking back with you and following all the great work that you'll be doing in the times ahead.Patrick Hsu (47:14):Thanks so much, Eric. It was such a pleasure to be here today. Appreciate the opportunity.*******************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly help fund our summer internship programs.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

In this engaging episode of BIO from the BAYOU, host James Zanewicz, JD, LLM, RTTP, sits down with Marc Malandro, PhD, to explore the impactful work of the Chan Zuckerberg Initiative (CZI). Founded in 2015, CZI initially broadly aims to tackle some of society's most pressing challenges to create a more inclusive, just, and healthy future. Having announced a next-phase on being a science-forward organization in January of 2024, Malandro is an increasingly key figure in CZI's ongoing initiatives (at the time of the interview as VP of Science Operations and now serving as Chief Operating Officer for the entire organization). Malandro also delves into the BioHub Network, which empowers scientists to pursue bold, high-risk ideas, and emphasizes the crucial role of collaboration in driving scientific progress. This episode was recorded at Bio on the Bayou, an annual event in New Orleans that highlights academic science, biotech innovations, and startups from the Gulf South region.

Guests Eva Maxfield Brown | Boris Veytsman Panelist Richard Littauer Show Notes In this episode of Sustain, host Richard Littauer engages with guests Eva Maxfield Brown and Boris Veytsman to explore their co-authored paper, "Biomedical Open Source Software: Crucial Packages and Hidden Heroes." The paper focuses on identifying crucial but often overlooked software dependencies in biomedical research. The discussions delve into how the study used data from two million papers to map these dependencies, revealing both well-supported and undermaintained software components vital to scientific research. There's a conversation on the methodological challenges and the concept of "Nebraska packages," which are essential yet potentially undermaintained elements crucial to the software stack used in both industry and science. The conversation also covers broader implications for software sustainability, security, and future research directions, including improving how software contributions are tracked and recognized within scientific careers. Press download now to hear more! [00:01:47] Richard dives into the paper co-authored by Eva and Boris. Boris explains the origins of the paper, starting from a workshop at CZI aimed at accelerating science through sustainable software, leading to the analysis of software used in biomedical research. He highlights the focus on identifying crucial yet often unmentioned software dependencies in research software, which he labels as “unsung heroes.” [00:05:22] Boris provides findings from their study, noting that while many foundational packages were cited, there are significant packages that, despite their critical role, remain uncited. [00:06:43] Eva discusses the concept of “Nebraska packages,” which are essential yet potentially undermaintained components that are crucial to the software stack used in both industry and science. Also, she elaborates on the methodological challenges of determining which packages to include in their analysis, particularly in terms of dependencies that vary between different users and contexts. [00:09:42] Richard reflects on the broader implications of their discussion for the open source community, particularly in terms of software sustainability and security. Eva emphasizes the importance of security across all fields and discusses the potential impact of software bugs on scientific research and the need for robust software infrastructure. [00:12:04] Boris comments on the necessity of well-tested tools in the scientific community, given that many scientists may lack a strong background in software development and training. [00:13:47] Richard quotes from the paper discussing the absence of cycles in the network of software packages used in science, indicating a more robust design compared to general software. He questions this in light of earlier comments about scientists not being great at coding. [00:14:08] Eva explains that the paper's findings about acyclic dependencies (DAGs) might seem surprising given the common perception that scientific software is poorly developed. She notes that while scientists may not be trained in proper software packaging, the Python environment helps prevent cyclic dependencies. [00:17:31] Richard brings up “Katz centrality” which is discussed in the paper, and Boris clarifies that “Katz centrality” refers to a concept by Leo Katz on network centrality, explaining how it helps determine the importance of nodes within a network. [00:20:13] Richard questions the practical applications of the research findings, probing for advice on supporting crucial but underrecognized dependencies within software ecosystems. Eva addresses future research directions, including improving ecosystem matching algorithms for better accuracy in linking software mentions to the correct ecosystems. [00:22:50] Eva suggests expanding the research to cover more domains beyond biomedicine, considering different software needs across various scientific disciplines. Boris discusses the potential for targeted interventions to support underrecognized contributors in the scientific software community aiming to enhance their prestige. [00:27:22] Richard asks how the research team plans to map dependencies to individual contributors and track their motivations. Boris responds that while they have gathered substantial data from sources like GitHub logs, publishing this information poses ethical challenges due to privacy concerns. [00:28:45] Eva discusses her work on linking GitHub profiles to academic authors using ORCID identifiers to better track contributions to scientific software. [00:31:42] Richard brings up the broader impacts of their research, questioning whether their study on software packages centrality within the scientific community is unique or if there are similar studies at this scale. Eva acknowledges the need for more comprehensive studies and cites a previous study from 2015 that analyzed developer networks on GitHub. Boris adds that while there is extensive literature on scientific citation networks, the study of dependencies is less explored. [00:34:38] Find out where you can follow Boris and Eva's work and social medias online. Spotlight [00:37:06] Richard's spotlight is Deirdre Madeleine Smith. [00:37:29] Eva's spotlight is Talley Lambert. [00:38:02] Boris's spotlight is the CZI Collaborators. Links SustainOSS (https://sustainoss.org/) SustainOSS Twitter (https://twitter.com/SustainOSS?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor) SustainOSS Discourse (https://discourse.sustainoss.org/) podcast@sustainoss.org (mailto:podcast@sustainoss.org) SustainOSS Mastodon (https://mastodon.social/tags/sustainoss) Open Collective-SustainOSS (Contribute) (https://opencollective.com/sustainoss) Richard Littauer Socials (https://www.burntfen.com/2023-05-30/socials) Eva Maxfield Brown X/Twitter (https://x.com/evamaxfieldb) Eva Maxfield Brown Website (https://evamaxfield.github.io/) Eva Maxfield Brown GitHub (https://github.com/evamaxfield) Boris Veytsman X/Twitter (https://x.com/BorisVeytsman?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor) Boris Veytsman Mastodon (https://sfba.social/@borisveytsman) Boris Veytsman LinkedIn (https://www.linkedin.com/in/boris-veytsman-50a1162/) Chan Zuckerberg Initiative (CTI) (https://chanzuckerberg.com/) “Biomedical Open Source Software : Crucial Packages and Hidden Heroes” (arXiv) (https://arxiv.org/pdf/2404.06672) “A large dataset of software mentions in the biomedical literature” (arXiv) (https://arxiv.org/abs/2209.00693) xkcd Dependency comic 2347 (https://xkcd.com/2347/) Dataset Artefacts are the Hidden Drivers of the Declining Disruptiveness in Science (arXiv) (https://arxiv.org/abs/2402.14583) Directed acyclic graph (DAG) (https://en.wikipedia.org/wiki/Directed_acyclic_graph) Katz centrality (https://en.wikipedia.org/wiki/Katz_centrality) Sustain Podcast-Episode 136: Daniel S. Katz on The Research Software Alliance (https://podcast.sustainoss.org/guests/katz) Sustain Podcast-Episode 159: Dawn Foster & Andrew Nesbitt at State of Open Con 2023 (https://podcast.sustainoss.org/guests/nesbitt) Sustain Podcast-Episode 218: Karthik Ram & James Howison on Research Software Visibility Infrastructure Priorities (https://podcast.sustainoss.org/guests/james-howison) ORCID (https://orcid.org/) Mapping the Impact of Research Software in Science- A CZI Hackathon (https://github.com/chanzuckerberg/software-impact-hackathon-2023) Deirdre Smith Academia (https://pitt.academia.edu/DeirdreSmith) Talley Lambert GitHub (https://github.com/tlambert03) Credits Produced by Richard Littauer (https://www.burntfen.com/) Edited by Paul M. Bahr at Peachtree Sound (https://www.peachtreesound.com/) Show notes by DeAnn Bahr Peachtree Sound (https://www.peachtreesound.com/) Special Guests: Boris Veytsman and Eva Maxfield Brown.

There are countless barriers facing immigrant communities when it comes to finding success and economic security in the US. Today we hear from two women who are working tirelessly to level the playing field by reimagining capitalism. Lemonada's Hoja Lopez chats with Ruby Bolaria Shifrin, head of community at the Chan Zuckerberg Initiative, and Claudia Arroyo, executive director of the non-profit Prospera. They discuss the value of supporting latinx entrepreneurs and putting female-owned businesses at the forefront of their local economies. This episode is supported by the Chan Zuckerberg Initiative. The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society's toughest challenges — from eradicating disease and improving education, to addressing the needs of our local communities. CZI's mission is to build a more inclusive, just, and healthy future for everyone. To learn more, visit https://chanzuckerberg.com. Thank you to Prospera for joining this conversation. Prospera advances Latina economic empowerment through leadership development, entrepreneurship and cooperative business ownership. Prospera believes that when women are at the forefront of our local economies, entire communities thrive. To learn more and get involved, visit https://prosperacoops.org.See omnystudio.com/listener for privacy information.

#S10e96 - https://www.youtube.com/watch?v=MkCKK4Z7J2I   Rochester - Check.  I asked in #S10e132 to do this and you stepped up, thank you.  We hit 200!   Aparito time Fill this in: https://forms.gle/4EsW3wu8BG4TQrD7A    The intersection of biomarkers and repurposing: The latter could help us figure out which of the former to focus on which could be the difference between a drug making it.   Repurposing:  Friend message - “And I wanted to tell you about the worsening behavior with treatments: a friend of mine has a son with Dravet syndrome, and many years ago they started him on a drug that reduced the seizures quite a bit, and my friend used to say “with this new treatment cleaning his brain from all those EEG interferences, we are starting to see more of his personality… and we've realized that we don't like him”. Very harsh but very real to say”   Morning Video SM vs ASO vs AAV https://www.youtube.com/watch?v=-xp3kTsBz38   List of repurposed drugs: Ravicti® (glycerol phenylbutyrate) - https://www.youtube.com/watch?v=Rwwdifsu1g8 Butyrate - https://www.youtube.com/watch?v=hjl9Z5_uQws NAL - https://www.youtube.com/watch?v=TphYC3o2BJQ  Pamelor® (nortriptyline) - https://www.youtube.com/watch?v=z0BdjDaWiMs  Fycompa® (perampanel) - Need to have a webinar on this.   Fycompa ® story from middle market country, Fycompa + Depakine + Risperadone.  Wow.   Ethics. Is it ethical to sit back and let our kids suffer?   Thank you to Virginie who is helping with EEG grant and volunteers, we have her back from ciitizen!  Thank you to those working on CZI grant too!   Congratulations to Encarnation and the SYNGAP1 European Team for this coverage https://english.elpais.com/health/2024-02-12/unraveling-the-mystery-of-celias-inexplicable-disease.html   Ed said: Syngap1Stories Episode 26 guest Paulina Polanco - released 2/13. Includes her Family Day talk in Orlando. Syngap.Fund/Stories Cafe Syngap1 Episode 11 guest Claudio Diaz - released 2/17 Syngap.Fund/Cafe Get Ready for Sprint - save the date 4/27/24 - sign up your teams now; Rifton is giving away another adaptive tricycle to a team who raises >$500 - Syngap.Fund/Sprint24  https://www.rifton.com/  (9 teams signed up as of 2/23 - we had 28 teams in 2023;) Orlando Family Day VideosUploaded to YouTube (https://www.youtube.com/playlist?list=PLjpr3a14_ls3PKu4oB_aeU_tfyYLE6-jj)  Added to Paulina's blog recap of the day (https://curesyngap1.org/blog/syngap1-family-day-2023-a-beacon-of-hope/);  Videos include Science Day Recap as well as a separate video of Mike's recap on “Where are we now?”, a summary of how parents can prepare for what's coming in the next couple of years (https://youtu.be/-xp3kTsBz38?si=_qHKRsYz2uJDJR_F). SYNGAP1 Conference 2024 hosted by SRF - planning committee will start meeting soon; if interested in helping, contact stacey@curesyngap1.org #SyngapConf SYNGAP1 Sibling Shanaye, a High School senior, is using her platform as the 2023 Hodgeman County Miss Teen Pageant winner to spread the word about SYNGAP1, which affects her younger sister Addison.YouTube Video - https://youtu.be/4L32aPNMSeM?si=EqNEhROdzvfGZxEQ Addison's Warrior Story - https://curesyngap1.org/syngap-warriors/addison/ We teamed with Simons Searchlight for their annual Shine Your Searchlight Campaign - if you're not signed up with Simons yet, sign up now - https://www.simonssearchlight.org/ Sydney & Sandy in S. Africa for Rare-X Rare Disease Conference - https://x.com/sandysmith317/status/1757669120928047520?s=20 We're looking for state representatives and state advocates - fill out this form if you're interested - https://docs.google.com/forms/d/e/1FAIpQLSfPWiyvAPuKif-h2bbMBqUKVLMeOeK-ISehbM9PvnReXMRjZg/viewformState Representatives - provide a point of contact for SYNGAP1 families (especially newly diagnosed) in your state to assist with information about registries, studies, fundraising, and other resources State Advocates - help families in your state navigate difficult systems (education, healthcare, state services, legal, etc.)   Upcoming Rare Disease Day - join us in DC; two blog posts:Rare Disease Day 2024 - what is it and how can you help SYNGAP1? You Should Represent SYNGAP1 During Rare Disease Week on Capitol Hill #S10e96 - https://www.youtube.com/watch?v=MkCKK4Z7J2I   Fundraising Getting organized:MDBR 6/8 - link to 2023 blog https://curesyngap1.org/blog/mdbr-2023-everything-we-want-to-c-happening-for-syngap1-camaraderie-community-collaboration/  2nd annual Golf Tourn in Canada 6/8 CFTC early-mid Sept? Link to past events is here:  https://curesyngap1.org/events/fundraisers/cannonball-for-the-cure/  3rd annual Scramble 10/5 - link to past events is here:  https://curesyngap1.org/events/fundraisers/scramble-for-syngap-2023/  4th annual SRF Gala honoring Caren Leib 10/18 - link to past events is here:  https://curesyngap1.org/events/fundraisers/srf-gala-honoring-caren-leib/ 3rd SYNGAP1 Conference, hosted by SRF in LA - pre-register to receive updated info when it's ready https://Syngap.Fund/24Pre   Podcasts, give all of these a five star review! SRF Channel - https://podcasts.apple.com/us/channel/syngap1-podcasts-by-srf/id6464522917 Episode 134 of #Syngap10 - Feb 24, 2024 #epilepsy #autism #intellectualdisability #id #anxiety #raredisease #epilepsyawareness #autismawareness #rarediseaseresearch #SynGAPResearchFund #CareAboutRare #PatientAdvocacy #GCchat #Neurology #GeneChat

At How Women Lead, we strongly believe in women finding their voice and being unabashedly visible in what they do. But finding your voice and learning to use it for your mission does not come naturally to everyone. Liz Sklar, actress and Director at Stand & Deliver, helps leaders across all industries find their voice and use it to be effective, inspiring leaders. She's here today to talk about her journey, how you can find your unique voice, and much more! This week's episode 101 of How Women Inspire Podcast is about improving your communication skills to find your voice! In this episode of How Women Inspire Podcast, Liz Sklar is sharing the importance of choosing to believe in yourself and your voice and actionable steps you can take right now to take care of yourself in today's stressful world. In her work with clients including Genentech, Gilead, Twilio, Google, IVP, CZI, Waymo, and the Cartier Women's Initiative, Liz's work has crossed industries from pharma to finance and frequently focuses on leaders in the innovation economy. She is especially inspired by female entrepreneurs and executives and is invested in empowering them to harness their innate power and wisdom to further their careers and expand their missions. Liz has acted professionally in both film and theater, including leading roles at premier regional theaters such as the California Shakespeare Festival and American Conservatory Theatre.Some of the talking points Julie and Liz go over in this episode include:How Liz's experience in theatre informs her leadership coaching in the corporate world.Emphasizing the value of finding and showcasing one's authentic self.Managing stress and influencing without authority in the workplace.Empowering women leaders through empathy and public speaking.Thank you for listening! If you enjoyed this episode, take a screenshot of the episode to post in your stories and tag me!  And don't forget to follow, rate, and review the podcast and tell me your key takeaways!Learn more about How Women Inspire at https://www.howwomenlead.com/podcast CONNECT WITH LIZ SKLAR:LinkedInWebsiteStand & DeliverCONNECT WITH JULIE CASTRO ABRAMS:LinkedIn - JulieHow Women LeadHow Women InvestHow Women GiveInstagram - HWLLinkedIn - HWLFacebook - HWL

The Chan Zuckerberg Initiative (CZI) was founded in 2015 to help solve society's challenges and create an inclusive, just, and healthy future. Dr. Marc Malandro discusses his role within CZI's science initiative, and their mantras of "Build, Fund, and Do." He also explains the BioHub Network, which empowers scientists to pursue exciting ideas regardless of the risk, and the role collaboration plays in their ability to propel science forward. Episode hosted by James Zanewicz. This episode was recorded at BIO on the BAYOU, the annual symposium in New Orleans showcasing academic science, biotech, and startups from the entire Gulf South region.

In this episode, my guests are Mark Zuckerberg, CEO of Meta (formerly Facebook, Inc.), and his wife, Dr. Priscilla Chan, M.D., co-founder and co-CEO of the Chan Zuckerberg Initiative (CZI). We discuss how CZI plans to cure all human diseases by the end of this century by funding transformative projects and technologies at the intersection of biology, engineering, and artificial intelligence (AI). They describe their funding and development of CZI Biohubs and the progress already underway to accelerate the understanding of cell function, pathways, and disease. Then, Mark discusses social media, its impact on mental health, and new tools for online experiences. We also discuss Meta's virtual reality (VR), augmented and mixed reality tech, and how AI will soon completely transform our online and physical life experiences. This episode ought to interest anyone curious about biology, medicine, mental health, AI, and the future of technology and humanity. For the full show notes, including the episode transcript (available exclusively to Huberman Lab Premium members), please visit hubermanlab.com. Pre-sale password: HUBERMAN Thank you to our sponsors AG1: https://drinkag1.com/huberman Eight Sleep: https://eightsleep.com/huberman LMNT: https://drinklmnt.com/huberman InsideTracker: https://insidetracker.com/huberman Momentous: https://livemomentous.com/huberman The Brain Body Contract Tickets: https://www.hubermanlab.com/events Timestamps (00:00:00) Mark Zuckerberg & Dr. Priscilla Chan (00:02:15) Sponsors: Eight Sleep & LMNT; The Brain Body Contract (00:05:35) Chan Zuckerberg Initiative (CZI) & Human Disease Research (00:08:51) Innovation & Discovery, Science & Engineering (00:12:53) Funding, Building Tools & Imaging (00:17:57) Healthy vs. Diseased Cells, Human Cell Atlas & AI, Virtual Cells (00:21:59) Single Cell Methods & Disease; CELLxGENE Tool  (00:28:22) Sponsor: AG1 (00:29:53) AI & Hypothesis Generation; Long-term Projects & Collaboration (00:35:14) Large Language Models (LLMs), In Silico Experiments (00:42:11) CZI Biohubs, Chicago, New York (00:50:52) Universities & Biohubs; Therapeutics & Rare Diseases (00:57:23) Optimism; Children & Families (01:06:21) Sponsor: InsideTracker (01:07:25) Technology & Health, Positive & Negative Interactions (01:13:17) Algorithms, Clickbait News, Individual Experience (01:19:17) Parental Controls, Meta Social Media Tools & Tailoring Experience (01:24:51) Time, Usage & Technology, Parental Tools (01:28:55) Virtual Reality (VR), Mixed Reality Experiences & Smart Glasses (01:36:09) Physical Exercise & Virtual Product Development (01:44:19) Virtual Futures for Creativity & Social Interactions (01:49:31) Ray-Ban Meta Smart Glasses: Potential, Privacy & Risks (02:00:20) Visual System & Smart Glasses, Augmented Reality (02:06:42) AI Assistants & Creators, Identity Protection (02:13:26) Zero-Cost Support, Spotify & Apple Reviews, Sponsors, YouTube Feedback, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

In this week's episode, both of our stories are from CZI's Rare As One Project. CZI's Rare As One Project brings together rare disease patients and advocates in their quest for cures. Both of this week's stories are from Rare As One grantees who are sharing their stories and experiences navigating diagnosis and organizing their communities to accelerate research, identify treatments, and change the course of their diseases. Part 1: After ending up in the ER for the third time, Rachel Alvarez struggles to understand what's going on with her health. Part 2: As a young adult with muscular dystrophy, Monkol Lek refuses to give up on his ambitions. Rachel Alvarez was diagnosed at birth with an unspecified neuromuscular condition, finally confirmed in 2009 as congenital muscular dystrophy. After graduating from California Polytechnic University, she spent her early career working in healthcare finance and operations. She joined Cure CMD as a volunteer when it was founded in 2008, and then as its first employee in 2012. Rachel continues to work for and on behalf of families living with congenital muscular dystrophy, to not only support their current needs, but to help ensure treatments in the foreseeable future for this group of ultra-rare conditions. Monkol Lek is an Assistant Professor at Yale University and runs a research lab that is dedicated to the genetics of muscle diseases. He grew up in Sydney and in his 20s received a diagnosis of muscular dystrophy, which motivated him to re-train and receive a PhD at the University of Sydney. He then migrated to Boston to train in human genetics and genomic technologies before starting his own lab at Yale. During his free time he likes to randomly complain on twitter, play computer games and hang out with his three rescue dogs! Learn more about your ad choices. Visit podcastchoices.com/adchoices

In this episode, Ana and Jeffrey discuss Ana's career journey, how she was drawn into the criminal justice reform, and how she's ended up going further than she even could have dreamt. Watch this episode on YouTube: https://youtu.be/WROp4iIBFFs Host: Jeffrey M. Zucker Producer: Kait Grey Editor: Nick Case Learn more: Recording date: 2/28/23 Ana: https://twitter.com/anarzamora https://www.linkedin.com/in/ana-zamora-6180ab17/ The Just Trust: https://www.thejusttrust.org/ https://twitter.com/thejusttrust https://www.facebook.com/TheJustTrust/ https://www.instagram.com/thejusttrust/ Other resources: https://www.openhousesf.org/ Ana: Until I crossed over into philanthropy in 2018, I spent my career fighting on the front lines of criminal justice reform—as an organizer, advocate, and campaigner. I've been in the trenches of this work when we lost way more than we won. I know the deep, painful sting of losing a major campaign that you've thrown your whole heart into. I also know what it feels like to be part of progress. It's these experiences that built my advocacy chops and taught me that the pathway to real change is crooked, rife with setbacks, and that no map exists to help you traverse it. My journey began in an administrative role with the California Appellate Project, an organization that provides legal services to people in California facing execution. There I learned about the harm and stigma that our punitive, unforgiving system has on communities and families, including my own. I then spent the next ten years working at the ACLU, ultimately as director of criminal justice reform. Using integrated advocacy, I worked to advance issues including sentencing reform, reducing use of the death penalty, legislative and administrative reforms around wrongful convictions, and greater prosecutorial accountability through voter education and engagement. During these years, I also served in leadership roles in two California ballot measures: as Deputy Campaign Manager for Yes on 34 in 2012 and as Campaign Manager for No on 66 in 2016. And I launched the first ever statewide prosecutor accountability campaign, simply called: “Meet Your DA.” In my advocacy life, I was deeply frustrated with the extreme lack of resources in our movement—especially for organizations with directly impacted leaders. I saw philanthropy as a critical unlock and eventually moved into a new role as director of criminal justice reform at the Chan Zuckerberg Initiative (CZI), which became one of the largest funders of frontline criminal justice reform work in the country—a $143 million portfolio in just under three years. My team at CZI backed key wins like Measure 110 in Oregon to decriminalize all drug possession; helped defeat Proposition 20 in California, which sought to roll back key justice reforms; funded the Clean Slate Initiative, supporting record-clearing policies for millions of people in Pennsylvania, Utah, Michigan, and other states; and, importantly, supported countless reform and organizing efforts led by directly impacted groups, in states often passed over like West Virginia, Kentucky, and North Carolina. In my personal life, I am proud to serve on the Board of Directors of Openhouse in San Francisco, which serves LGBTQ+ seniors. It's an honor and a privilege to now lead The Just Trust—where I get to wear all of my hats and channel the stings of losses, the glory of wins, and the hope that I feel from across this powerful, diverse, ever-evolving fight for justice, safety, and wellbeing.

The CZ Biohub's inspiring story began when Priscilla Chan asked Stephen Quake a seemingly impossible question: “Is it possible to cure, prevent, and manage disease in our children's lifetime?”. In 2016, the Chan Zuckerberg Initiative, founded by Priscilla and Mark Zuckerberg, set out to answer that question with a bold new mission. On the final installment of our CZ Biohub series, Priscilla and Stephen join Nate to talk about the work being done at Biohub, and how understanding human biology is the key to unlocking powerful medical treatments and cures. Through their commitment to the cause, they are showing that anything is possible. Priscilla Chan is co-founder and co-CEO of the Chan Zuckerberg Initiative (CZI). Stephen Quake is Head of Science at the Chan Zuckerberg Initiative, where he oversees CZI's science grant programs, technology development, and the CZ Biohub Network. Stephen is also a professor at Stanford University. Learn more about CZ Biohub: https://www.czbiohub.org/about/#history-amp-mission Listen to more episodes from our CZ Biohub series: https://theshowaboutscience.com/2023/02/12/099-accelerating-science-to-eradicate-disease-with-priscilla-chan-and-stephen-quake/ Connect with The Show About Science:  Instagram: https://www.instagram.com/showaboutscience Facebook: https://www.facebook.com/theshowaboutscience YouTube: https://www.youtube.com/showaboutscience Twitter: https://www.twitter.com/natepodcasts LinkedIn: https://www.linkedin.com/ Loved this episode? Leave us a review and rating wherever you listen to podcasts!

In this episode, we're joined by Broad Institute Senior Group Leader and Head of the Cimini Lab Imaging Platform Beth Cimini, Ph.D., for a lesson in high-content image analysis! Cimini is a subject matter expert who shares her knowledge to explain how high-content image analysis works and how it pertains to cell painting. Key Learning Points:The types of research high-content imaging is ideal for The process of developing an assay for a high-content imaging approachWhat you need to know to use high-content imaging in your research About Beth Cimini, Ph.D.Cimini is a senior group leader, CZI imaging scientist and the head of the Cimini Lab in the Imaging Platform at the Broad Institute in Cambridge, MA. After completing her undergraduate research in visual neuroscience at Boston University, Cimini obtained a Ph.D. in Biochemistry and Molecular Biology at the University of California San Francisco, where she studied the difference between splicing variants of the telomere master scaffolding protein TIN2.  She created and directs the Platform's Postdoctoral Training Program in Bioimage Analysis, and also leads the Broad efforts toward community engagement and driving biological projects for the Center for Open Bioimage Analysis.Stay connected with SLAS:Online at www.slas.orgFacebookTwitter @SLAS_OrgLinkedInInstagram @slas_orgYouTubeAbout SLAS:SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.  For more information about SLAS, visit www.slas.org.SLAS publishes two peer-reviewed and MEDLINE-indexed scientific journals, SLAS Discovery and SLAS Technology. For more information about SLAS and its journals, visit www.slas.org/publications.For Students:Visit the SLAS Student Resources to find information on student-focused SLAS awards, grants, scholarships, digital educational content, podcasts and more.Upcoming SLAS Events: SLAS2023 International Conference and Exhibition February 25 - March 1, 2023 San Diego, CA, USA SLAS 2023 Building Biology in 3D Symposium 20-21 April 2023 Cambridge, United Kingdom SLAS Europe 2023 Conference and Exhibition 23-26 May 2023 Brussels, Belgium

Comprehensive Summary Report of the coup d'etat against WE THE PEOPLE Of These United States A Constitutional Republic By The People For The People.Share with as many as possible!!!UNagenda2030 Event 201. WEF. Gates. John Hopkins. Biz. CDC CCP. Pompeo admits live exercise. Nov3 2020. Jan 6 2021 Electors. 100+ Congressional members to reject then false flag by Pelosi Schummer Nadler Schiff McConnell Lindsey Graham & others. Dominion. Zuckerberg. CZI. Sec of States. GovernorsPysops companies from JoBama admin________________________NEO420 = Real News + Real Information for WE THE PEOPLEWE THE PEOPLE are at war with the deepstate criminal cabal!!!Turn off your tv, radio, and stop listening to paid professional liars spreading propaganda.***SUPPORT Independent Free Speech Reporting***Thank you for the SUPPORT & SHARING the TRUTH!!!Go to GOD for discernment and wisdom.Know the Truth as the Truth will make you free! (John 8:32)___________________________Listen and learn as we have an extensive coverage within our reporting and analysis.  The link is here http://neo420.com/talks-podcast/The link to our video channel is here. https://odysee.com/@NEO420TALKS:4The Viral Delusionhttp://www.theviraldelusion.com/IT IS TIME FOR WE THE PEOPLE OF THE WORLD TAKE DOWN the criminal cabal. WE know who they are, and now it is time to bring them to JUSTICE!!!_______________________________NEVER FORGET!!!9/11 was a day that global*cabal*conspired to take our freedoms!!!Rumsfeld admitted $2.3 Trillion missing from Pentagon.  https://odysee.com/@NEO420TALKS:4/rumsfeld-2.1Trillionunaccountedforb-ccriminalsstoleit:7Planes did NOT bring down the two towers.AE911Truth.orgGeorge Bush Sr was CIA director before being Vice President then President. MANY are a part of this crime against US.Towers that fell:-Building 1-Building 2-Building 7 (seldom reported even though BBC reporter reported building down before it happened) https://www.youtube.com/watch?v=J0VFMqiSupport the show

On this edition of Closer Look: Four Historically Black Medical Colleges are set to expand genomic research thanks to $11 million grants for each school from the Chan Zuckerberg Initiative (CZI). Dr. Ivory Dean, with CZI and Dr. Rick Kittles with Morehouse explain how the school's $11 million grant will be used.Plus, East Point City Councilmember Joshua Butler says he has a plan to bring a hospital back to South Fulton County.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Um médico com veia empreendedora que criou duas empresas na área de saúde. A segunda delas, a Beep Saúde, acaba de receber um investimento Série C, liderado pelo fundo CZI, de Mark Zuckerberg, fundador do Grupo Meta, e sua esposa Priscila Chan.A startup com foco em vacinação é líder em saúde domiciliar no Brasil, e destinará os novos recursos para impulsionar o crescimento e atingir o breakeven (um indicador que sinaliza o empate entre as receitas e as despesas de um negócio). A projeção de faturamento para 2023 é de R$ 250 milhões.“Conseguimos trazer gente bacana para viver o nosso sonho. Fomos apresentados e após um processo muito diligente, muito criterioso, vamos receber o fundo de ninguém menos que o Mark Zuckerberg. Ele a esposa tem uma iniciativa para a área. Ela é médica, pediatra, e a conexão com a Beep foi clara”, completa Corteze. Ex-médico do Corpo de Bombeiros, Corteze é o convidado deste episódio especial do Zero ao Topo, patrocinado por XP Empresas. Ele criou a primeira empresa com 25 anos, a BR Med, de saúde ocupacional, e foi com a renda dela que investiu do próprio bolso para fundar a Beep.

Guest Melissa Mendonça Panelists Richard Littauer | Amanda Casari Show Notes Hello and welcome to Sustain! The podcast where we talk about sustaining open source for the long haul. Today, we are so excited to have a wonderful guest, Melissa Mendonça, joining us. Melissa is a Senior Developer Experience Engineer at Quansight, where she focuses more on developer experience and contributor experience. Today, we'll hear all about Quansight and the focus for Melissa's role as a Developer Experience Engineer. Melissa tells us about a grant they are working on with CZI that focuses on NumPy, SciPy, Matplotlib, and pandas, she shares several ideas on what can be done to make people feel seen and heard, and we hear her thoughts on what the future of community management and community development looks like for people entering the role of these projects. Go ahead and download this episode now to hear more! [00:01:25] Melissa tells us her background and her role at Quansight. [00:03:41] When Melissa made the decision to switch from one role to another, Amanda asks if that was her plan or if she learned that the skills that she needed to get things done changed over time. [00:06:10] We find out what the focus is for Melissa's role as a Developer Experience Engineer and what she does on a day-to-day basis. [00:08:43] As Melissa was talking about her projects that they work on at Quansight, Amanda wonders if that's the majority of her portfolio, or if she works across different kinds of projects. We learn about the current grant they are working on with CZI that focuses on NumPy, SciPy, Matplotlib, and pandas. [00:13:18] We learn about the funding model and how sustainable it is. [00:16:20] Melissa shares some great ideas on how we can put more effort into making people feel seen and heard. [00:19:26] Melissa details some things she learned with the open source projects and things she recommends for others with large established projects. [00:22:44] Amanda talks about a 2020 paper that was released in nature called “Array programming with NumPy,” and Melissa gives us her perspective on what happened with the community in 2020, if things have changed, and what needs to be addressed. [00:27:09] Find out how CZI got involved with Melissa's work, what their goals are, and how she's changing in order to adapt towards those goals. [00:31:32] Melissa shares her thoughts on what the future of community management and community development looks like for people who are entering the role for those projects. [00:36:40] We hear more about Python Brasil 2022 that's coming up. [00:38:05] Find out where you can follow Melissa online and learn more about her work. Quotes [00:02:49] “Since Quansight is a company very focused on sustaining and helping maintain open source projects, we are trying to help new contributors, people who want to do the move from contributor to maintainer, understanding what that means, and how we can help them get there, and how we can help improve leadership in our open source projects.” [00:11:53] “This is one of the barriers that we want to break, is that making sure that people understand that these are important, they are core projects in the scientific Python ecosystem, but at the same time they are projects just like any other.” [00:12:17] “I think experience of working with projects that are so old and big has taught me a lot about the dynamics of how people work and how new people try to join these projects and how we can improve on that.” [00:16:41] “We need to make sure that people who do contribution outside of code are credited and that they are valued inside open source projects.” [00:18:20] “I think we should think about diversifying these paths for contribution, but for that we need to go beyond GitHub. We need to go beyond the current metrics that we have for open source, we need to go beyond the current credit system and reputation system that we have for open source contributions.” [00:30:38] “Community managers are not second-class citizens.” Spotlight [00:39:21 Amanda's spotlight is a 2014 paper from MSR called, “The Promises and Perils of Mining GitHub.” [00:40:48] Richard's spotlight is the book, Don't Sleep, There Are Snakes, by Daniel Everett. [00:41:52] Melissa's spotlights are Ralf Gommers and Scientific Python initiative. Links SustainOSS (https://sustainoss.org/) SustainOSS Twitter (https://twitter.com/SustainOSS?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor) SustainOSS Discourse (https://discourse.sustainoss.org/) podcast@sustainoss.org (mailto:podcast@sustainoss.org) Richard Littauer Twitter (https://twitter.com/richlitt?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor) Amanda Casari Twitter (https://twitter.com/amcasari?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor) Melissa Mendonça Twitter (https://twitter.com/melissawm) Melissa Mendonça LinkedIn (https://br.linkedin.com/in/axequalsb) Melissa Mendonça GitHub (https://melissawm.github.io/) Quansight (https://quansight.com/) Quansight Labs (https://labs.quansight.org/) Quansight Lab Projects (https://labs.quansight.org/projects) Quansight Labs Team (https://labs.quansight.org/team) Sustain Podcast-Episode 57: Mikeal Rogers on Building Communities, the Early Days of Node.js, and How to Stay a Coder for Life (https://podcast.sustainoss.org/guests/mikeal) Sustain Podcast-Episode 85: Geoffrey Huntley and Sustaining OSS with Gitpod (https://podcast.sustainoss.org/85) Advancing an inclusive culture in the scientific Python ecosystem (CZI grant for NumPy, SciPy, Matplotlib, and Pandas (https://figshare.com/articles/online_resource/Advancing_an_inclusive_culture_in_the_scientific_Python_ecosystem/16548063) Sustain Podcast-Episode 79: Leah Silen on how NumFocus helps makes scientific code more sustainable (https://podcast.sustainoss.org/79) NumPy (https://numpy.org/) SciPy (https://scipy.org/) Matplotlib (https://matplotlib.org/) pandas (https://pandas.pydata.org/) Sustain Podcast-Episode 64: Travis Oliphant and Russell Pekrul on NumPy, Anaconda, and giving back with FairOSS (https://podcast.sustainoss.org/guests/oliphant) Tania Allard Twitter (https://twitter.com/ixek?lang=en) Array programming with NumPy (nature) (https://www.nature.com/articles/s41586-020-2649-2) Python Brasil 2022 (https://2022.pythonbrasil.org.br/) “The Promises and Perils of Mining GitHub,” by Eirini Kalliamvakou, Georgios Gousios, Kelly Blincoe, Leif Singer, Daniel M. German, Daniela Damian (https://kblincoe.github.io/publications/2014_MSR_Promises_Perils.pdf) “The Promises and Perils of Mining GitHub,” by Eirini Kalliamvakou, Georgios Gousios, Kelly Blincoe, Leif Singer, Daniel M. German, Daniela Damian (ACM Digital Library) (https://dl.acm.org/doi/10.1145/2597073.2597074) Daniel Everett (Wikipedia) (https://en.wikipedia.org/wiki/Daniel_Everett#Don't_Sleep,_There_Are_Snakes:_Life_and_Language_in_the_Amazonian_Jungle) Excerpt: ‘Don't Sleep, There Are Snakes' (npr) (https://www.npr.org/2009/12/23/121515579/excerpt-dont-sleep-there-are-snakes?t=1661871384424) Ralf Gommers (GitHub) (https://github.com/rgommers) Scientific Python (https://scientific-python.org/) Credits Produced by Richard Littauer (https://www.burntfen.com/) Edited by Paul M. Bahr at Peachtree Sound (https://www.peachtreesound.com/) Show notes by DeAnn Bahr Peachtree Sound (https://www.peachtreesound.com/) Special Guest: Melissa Mendonça.

Esse episódio foi gravado em Inglês.Vivian Wu leads impact investment as Managing Partner Ventures at Chan Zuckerberg Initiative (CZI).  Founded in 2015, CZI hopes to solve some of society's toughest challenges with a combination of technology, grantmaking, and impact investing.  Vivian has over two decades of experience in venture capital and private equity, and, at CZI, she led investments in education companies such as Descomplica, Age of Learning, Andela, and Byju's. She has an MBA from Harvard Business School, and a dual degree in Finance and History from the University of Pennsylvania. In this episode,  we listen to Vivian's story, as well as discuss CZI Ventures's investment strategies, impact measurement,  and her vision in education and Latin America. Tune in!

Walking the halls of Chicago International Charter School in the city's Bucktown neighborhood, you're likely to hear some interesting terms. Empathy interviews. Restorative justice. It's all part of the school's social emotional learning approach. But what does this teaching terminology look like in practice? In this episode of Building Classroom Connections, from TODAY and sponsored by the Chan Zuckerberg Initiative, we speak with students and educators about how SEL affects their experiences at school and outside the classroom.

Priscilla Chan, CEO of the Chan Zuckerberg Initiative, credits her teachers with inspiring her academic success. And so do the students at Valor College Prep, a Nashville school with a whole child approach to education supported in part by her organization. In this episode of Building Classroom Connections, from TODAY and sponsored by the Chan Zuckerberg Initiative, NBC's Morgan Radford talks to Chan about CZI's commitment to education initiatives and the importance of fostering strong student-teacher relationships. And, students and teachers tell their stories, about the kind of collaborative strategies helping them succeed together.

Students are heading back to school across America after a challenging few years which brought major changes to their lives. One learning framework increasingly implemented in schools is called social emotional learning, or SEL. In Building Classroom Connections, from TODAY and sponsored by the Chan Zuckerberg Initiative, we dive into just what SEL looks like in practice and explore whether this framework is the future of education.

At the beginning of June we were invited to moderate a panel at the Chan Zuckerberg Initiative Rare as One Annual Meeting in San Diego, CA. Most of the time diagnosis of a rare disease comes out of the blue and includes life altering, and life shortening symptoms.  The effect of which leave familiy members and friends to manage care and figure out how they might solve the problem.  Many times this means starting a nonprotit organization to advance science toward a treatment and cure.  Patients, parents and friends run these organizations with little to no budget or training.  These heroic efforts make slow progress while testing the resolve of their leaders who are constantly operating at the edge of their emotional, and physical capacity. The CZI Rare as One Program provides funding and training to build or expand research networks as well as increase organizational infrastructure to support this important work. The program started in 2019 and this was the first in person meeting of the 50 grantee organizations that make up the Rare as One Network.  It was an emotional time as the grantees continued to learn and laugh together in 3D instead of through a screen. We had the opportunity to moderate the closing session to talk about the incredible progress to date and the future of the program with three leaders of Rare as One,  Vice President, Science in Society at CZI, Tania Simoncelli Rare as One Program Manager, Heidi Bjornson-Pennell Rare as One Program Associate, Andra Stratton Enjoy the conversation.

Measure 110 (I might have said 101 in podcast, here is correction) was passed in Oregon with $500k provided by Chong Zuckerberg Initiative (czi). CZI is not in Oregon nor does either Chong or Zuckerberg live in Oregon. So, why would they fund this measure??? The answer is that they are part of the international criminal cabal that is working to destroy USA and bring it in as part of new world order which is a non regulated government to oversee the countries of the world without any oversight. That is criminal on every level known!!! It is modern slavery!!! Legal Drugs:- caffeine- alcohol- nicotineIllegal Drugs:- meth- oxy- cocaine- crack- othersCannabis & Hemp have been the largest search options on search engines for years and they were moving money away from criminal organizations and into real business owners/small business owners hands. Then the plandemic stopped that!!! And pfizer bought a canna research company for billions with WE THE PEOPLE money. That is criminal!!! WE have to stop the criminals!!!ALL the criminals involved in this coup d'etat against WE THE PEOPLE must be held accountable for their actions. And pay with their lives!!!________________________WE THE PEOPLE are at war with the deepstate criminal cabal!!!Turn off your tv, radio, and stop listening to paid professional liars spreading propaganda.***SUPPORT Independent Free Speech Reporting***NEO420 = News Intelligence Entertainment- Real News + Real Information- Here is our direct Paypal account.https://www.paypal.com/donate/?hosted_button_id=URXRDL6AJ8H7GThank you for the SUPPORT & SHARING the TRUTH!!!Go to GOD for discernment and wisdom.Know the Truth as the Truth will make you free! (John 8:32)___________________________Please go back and listen to our previous episodes all on our website for free. The "dots" have been provided, and you can see exactly what is happening, who did it, why, and how to defeat the system.Listen and learn as we have an extensive coverage.  The link is here http://neo420.com/talks-podcast/The link to our video channel is here. https://odysee.com/@NEO420TALKS:4The Viral Delusionhttp://www.theviraldelusion.com/IT IS TIME FOR WE THE PEOPLE OF THE WORLD TAKE DOWN the criminal cabal. WE know who they are, and now it is time to bring them to JUSTICE!!!_______________________________NEVER FORGET!!!9/11 was a day that global*cabal*conspired to take our freedoms!!!Rumsfeld admitted $2.3 Trillion missing from Pentagon.  https://odysee.com/@NEO420TALKS:4/rumsfeld-2.1Trillionunaccountedforb-ccriminalsstoleit:7Planes did NOT bring down the two towers.AE911Truth.orgGeorge Bush Sr was CIA director before being Vice President then President. MANY are a part of this crime against US.Towers that fell:-Building 1-Building 2-Building 7 (seldom reported even though BBC reporter reported building down before it happened) https://www.youtu

Last week, Mark Zuckerberg and Pricilla Chan announced their second large set of charitable gifts into the carbon removal field in the last six months. Specifically, the Chan-Zuckerberg Initiative announced $44 million in grants towards CDR. Combined with the $23 million they gave in October of 2021, the couple has given $67 million to support carbon removal in the last five months. They join other billionaires like Jeremy Grantham and Elon Musk, whose giving has shown they also see CDR as an important part of the climate fight. While a few foundations, such as CZI, have the resources to look deeply at supporting the carbon removal industry, many corporations rely on net-zero plans that lack full detail about carbon accounting and emissions reductions plans. A report released earlier this month by the New Climate Institute and Carbon Market Watch found that the net-zero plans of 25 of the world's most valuable companies are not specific and don't explain how they'll reduce emissions by 2050. A new coalition announced last week aims to fill this alleged gap in credibility between corporate plans and real action. Microsoft and the Climateworks Foundation announced “Carbon Call,” a partnership between 20 corporates, non-profits, and research organizations. In a statement to Axios, the group is building what they call “a carbon ledger…a global dashboard that tells you what exactly is happening in terms of emissions,” in a statement . Signatories include Deloitte, GlaxoSmithKline, and the UN Environment Program. The coalition will use their pooled resources and expertise to improve the carbon accounting methodologies used in corporate emissions reporting. Ultimately, they hope this will allow corporate and national emission data to be accurate and directly comparable. In this week's business episode, hosts Radhika Moolgavkar, Susan Su, and Na'im Merchant discuss the CZI gifts, how Carbon Call aims to improve corporate emissions accounting, and the short supply of quality carbon removal available to meet the skyrocketing demand. --- Send in a voice message: https://anchor.fm/carbonremovalnewsroom/message Support this podcast: https://anchor.fm/carbonremovalnewsroom/support

Dr. Stephani Otte, Ph.D is Science Program Officer, Imaging, at the Chan Zuckerberg Initiative (https://chanzuckerberg.com/), who leads the organization's Imaging program and is focused on the creation, dissemination, optimization, and standardization of transformative imaging technologies. Prior to CZI, Dr. Otte was Director of Science at a neuro-technology / microscopy company, Inscopix, involved in accelerating brain science and innovating mini-scope microscope solutions for real-time mapping of the human brain and it's circuits. Dr. Otte received her Ph.D. in Neuroscience at the University of California, San Diego, and did postdoctoral fellowships in systems neuroscience at the Salk Institute and University of California, Berkeley. The Chan Zuckerberg Initiative is an organization established and owned by Dr. Priscilla Chan and her husband, Facebook founder Mark Zuckerberg, with a focus on science, education, immigration reform, housing, criminal justice, and other local issues, with a mission to "build a more inclusive, just, and healthy future for everyone" and to "advance human potential and promote equality in areas such as health, education, scientific research and energy".

PC explains the criminal cabal shift toward the 420 community. The criminals are trying to get conservative states to approve cannabis use even when The People of that state do not want it. The criminals in politics, media, business, government, and elsewhere want the passage of cannabis as they use it "as a gateway" to other more serious crimes and destruction of the state, to which The People of the state have to deal with. Measure 110 (https://www.oregonlegislature.gov/lpro/Publications/Background-Brief-Measure-110-(2020).pdf?ID=1459 ) was funded by the CZI by $500k to decriminalize drugs completely. CZI doesn't have an office nor does Chan or Zuckerberg live in Oregon yet they paid to get drugs legalized. And large amounts are now considered a minor misdemeanor charge. Drug dealers and the cia love this. But The People of Oregon are having to deal with all the criminality, lawlessness, drug addicts, and the government doesn't care. The criminals want that revenue from cannabis as they will get their criminal hands in it and it won't do a bit of good for the state. The Measure 110 "alleged" savings and the cannabis revenue will go into a "grant" to use for addition and recovery. THIS MAKES NO SENSE!!! You are going to let the person become addicted then the money of The People has to pay for the recovery of the drug addict. And this is after the drug addict stole from The People to buy drugs for their addiction. THIS IS CRIMINAL IN EVERY WAY!!! ARREST THE CRIMINALS IN GOVERNMENT!!!Please go back and listen to our previous episodes all on our website for free. Listen and learn as we have an extensive coverage within our reporting and analysis.  The link is here http://neo420.com/talks-podcast/And the link to our video channel is here. https://odysee.com/@NEO420TALKS:4IT IS TIME FOR WE THE PEOPLE OF THE WORLD TAKE DOWN the criminal cabal. WE know who they are, and now it is time to bring them to JUSTICE!!!________________________________________________________________________JOIN US TODAY IN EXPOSING THE CRIMINALS & ARRESTING THE CRIMINALS!!!"STAND FOR SOMETHING OR DIE FOR NOTHING"Go to GOD for discernment and wisdom. Know the Truth as the Truth will make you free! (John 8:32)__________________________________________________________________________NEVER FORGET!!!9/11 was a day that global*cabal*conspired to take our freedoms!!!Rumsfeld admitted $2.3 Trillion missing from Pentagon.  https://odysee.com/@NEO420TALKS:4/rumsfeld-2.1Trillionunaccountedforb-ccriminalsstoleit:7Planes did NOT bring down the two towers.AE911Truth.orgGeorge Bush Sr was CIA director before being Vice President then President. MANY are a part of this crime against US.Towers that fell:-Building 1-Building 2-Building 7 (seldom reported even though BBC reporter reported building down before it happened) https://www.youtube.com/watch?v=J0VFMqinkcs

One of the challenges various healthcare stakeholders face is making decisions based on limited and lagging data about the changing landscape. Komodo Health has collected a broad range of real-world data that allows it to capture a comprehensive view of patients moving through the healthcare system along with next-generation analytics to derive meaningful insights and drive decisions that improve patient outcomes. The company recently announced that it had entered into an agreement with the Chan Zuckerberg Initiative's Rare As One network to provide software and analytic tools to help patient advocacy organizations in the network accelerate diagnoses, improve care, and advance research. We spoke to Web Sun, co-founder and president of Komodo Health, its platform technology, its potential to improve decision-making in the healthcare arena, and how members of CZI's Rare As One network will be able to leverage its real-word data and analytic tools.

This month, Governor Gavin Newsom's administration reported a quarter of a million Californians experiencing homelessness requested help in 2020—numbers that skyrocketed from previous estimates in some Bay Area counties. The Golden State is lauded for its job opportunities and diverse population, but it's also the state with some of the highest housing and transportation costs in the nation. Now, Californians are demanding change, and a cross-sectional group of affordable housing and homelessness advocates created Roadmap Home 2030, a definitive plan to end homelessness and create affordable homes for all over the next 10 years. Housing California, the California Housing Partnership, and dozens of experts and advocates identified 57 policy solutions to create affordable homes, protect low-income renters, end homelessness and ensure racial equity. With their detailed plan of creative solutions, coupled with dedicated leadership, this ambitious group believes a better California is doable. The wealth gap and a shortage of affordable homes in the state prohibits Californians from building healthy and fulfilling lives. With considerable energy and influence, this coalition of housing advocates are seeking to make bold, structural change to create an equitable future where everyone has a safe place to live. Join our expert panel for a conversation about equity, change and the fight to dramatically shift the landscape on affordable housing and homelessness in the Golden State. About the Speakers Ruby Bolaria-Shifrin is director of housing affordability for the Chan Zuckerberg Initiative (CZI). As part of CZI's commitment to ensuring access to safe, stable and affordable housing, she works with community leaders, advocates, researchers, policymakers and investors to help more people find housing that meets their needs. As one of San Francisco's voices in Sacramento, Assemblymember David Chiu is an outspoken advocate for housing reform and equity. He currently chairs the California State Assembly's Committee on Housing and Community Development. With more than 20 years of leadership and work in the field, Tomiquia Moss brings expertise in the issues of housing, public policy and community development. She is the founder and chief executive of All Home, a Bay Area-focused nonprofit. Prior to All Home, Tomiquia served as chief of staff for Oakland Mayor Libby Schaaf and as executive director for the HOPE SF initiative under the late San Francisco Mayor Ed Lee. A native Angeleno, Tunua Thrash-Ntuk is the executive director of Los Angeles Local Initiatives Support Corporation (LA LISC). She is a seasoned community and economic development practitioner of more than 15 years, with both nonprofit and private sector experiences. Her strengths range from community advocacy to asset and real estate development around neighborhood revitalization. SPEAKERS Ruby Bolaria-Shifrin Director of Housing Affordability, Chan Zuckerberg Initiative David Chiu California State Assemblymember, 17th District Tomiquia Moss Founder and Chief Executive, All Home Tunua Thrash-Ntuk Executive Director, Los Angeles Local Initiatives Support Corporation (LA LISC) Molly Solomon Reporter for Housing Affordability, KQED Public Media—Moderator In response to the COVID-19 pandemic, we are currently hosting all of our live programming via YouTube live stream. This program was recorded via video conference on April 27th, 2021 by the Commonwealth Club of California. Learn more about your ad choices. Visit megaphone.fm/adchoices

This month, Governor Gavin Newsom’s administration reported a quarter of a million Californians experiencing homelessness requested help in 2020—numbers that skyrocketed from previous estimates in some Bay Area counties. The Golden State is lauded for its job opportunities and diverse population, but it’s also the state with some of the highest housing and transportation costs in the nation. Now, Californians are demanding change, and a cross-sectional group of affordable housing and homelessness advocates created Roadmap Home 2030, a definitive plan to end homelessness and create affordable homes for all over the next 10 years. Housing California, the California Housing Partnership, and dozens of experts and advocates identified 57 policy solutions to create affordable homes, protect low-income renters, end homelessness and ensure racial equity. With their detailed plan of creative solutions, coupled with dedicated leadership, this ambitious group believes a better California is doable. The wealth gap and a shortage of affordable homes in the state prohibits Californians from building healthy and fulfilling lives. With considerable energy and influence, this coalition of housing advocates are seeking to make bold, structural change to create an equitable future where everyone has a safe place to live. Join our expert panel for a conversation about equity, change and the fight to dramatically shift the landscape on affordable housing and homelessness in the Golden State. About the Speakers Ruby Bolaria-Shifrin is director of housing affordability for the Chan Zuckerberg Initiative (CZI). As part of CZI’s commitment to ensuring access to safe, stable and affordable housing, she works with community leaders, advocates, researchers, policymakers and investors to help more people find housing that meets their needs. As one of San Francisco’s voices in Sacramento, Assemblymember David Chiu is an outspoken advocate for housing reform and equity. He currently chairs the California State Assembly’s Committee on Housing and Community Development. With more than 20 years of leadership and work in the field, Tomiquia Moss brings expertise in the issues of housing, public policy and community development. She is the founder and chief executive of All Home, a Bay Area-focused nonprofit. Prior to All Home, Tomiquia served as chief of staff for Oakland Mayor Libby Schaaf and as executive director for the HOPE SF initiative under the late San Francisco Mayor Ed Lee. A native Angeleno, Tunua Thrash-Ntuk is the executive director of Los Angeles Local Initiatives Support Corporation (LA LISC). She is a seasoned community and economic development practitioner of more than 15 years, with both nonprofit and private sector experiences. Her strengths range from community advocacy to asset and real estate development around neighborhood revitalization. SPEAKERS Ruby Bolaria-Shifrin Director of Housing Affordability, Chan Zuckerberg Initiative David Chiu California State Assemblymember, 17th District Tomiquia Moss Founder and Chief Executive, All Home Tunua Thrash-Ntuk Executive Director, Los Angeles Local Initiatives Support Corporation (LA LISC) Molly Solomon Reporter for Housing Affordability, KQED Public Media—Moderator In response to the COVID-19 pandemic, we are currently hosting all of our live programming via YouTube live stream. This program was recorded via video conference on April 27th, 2021 by the Commonwealth Club of California. Learn more about your ad choices. Visit megaphone.fm/adchoices

We have a very special episode this week because we’re sharing the vulnerable story of how one of our guests was subsequently fired from a high profile role in the US and how she navigated her way through the dark times that followed. That guest is Heidi Hackemer and what she shares in this episode is so generous and valuable for all of us to hear; after all nothing is permanent and plans fall over on a regular basis. Heidi is a leading creative who had her own brand agency in New York and also headed up the Creative Studio at the philanthropic Chan Zuckerberg Initiative (CZI) in California. Not long after our first conversation with Heidi in July 2018 things went wrong, very wrong. Heidi was fired from CZI and not only that, when she got back to New York, she had to close her brand strategy agency, W&W too. We learnt about this because Heidi wrote an extremely brave and vulnerable article on Medium (link below) describing what had happened and how low she was feeling.Admiring her generous honesty, we reached out to her just as COVID was taking hold everywhere round the world last year. Heidi agreed to speak with us.After our conversation, we made a decision not to publish the interview last year, as it just felt too raw. With Heidi’s permission, we’ve all agreed that now is the right time to share the story she has been so generous in sharing with us. She’s well and truly bounced back from the lows she describes and is now the Executive Creative Director for North America at the booming global company, Oatly. In this episode Heidi shares: How, after being fired, she initially couldn’t stop worrying about moneyHer advice for others who lose their jobsHeidi’s generous sharing of all the things she did to pull herself out of depression and bounce back, And the inspiring reason she shared her extraordinary piece on MediumEven if you are securely employed right now, we really recommend you listen to this unique conversation. And if you know someone who’s lost their job make sure they listen to this too! They’ll thank you later. Enjoy this episode with the generous, and very thoughtful, Heidi Hackemer.Useful LinksHeidi on LinkedInMedium article that prompted this second interviewHeidi on TwitterHeidi on InstagramOatly website See acast.com/privacy for privacy and opt-out information.

Happy Black History Month! We're thrilled to invite Iyinoluwa Aboyeji to sit in the genius chair for our first episode of Black Genius, season 2. Aboyeji's interview opens the Harambeans 10×10 series through which we'd be highlighting the stories of 10 Harambeans building Africa's future through visionary, market-creating, global enterprises. Aboyeji says: "personal success cannot insulate from the failures of your society. I don't see entrepreneurship as a way to personally enrich myself but as a tool for social change. It must be done not just for profit or personal interest but most importantly as a service in the public interest." The first Black Genius to be featured in the Harambe series, Iyinoluwa Aboyeji, made history when the startup he co-founded, Andela, received a $24 Million investment from Mark Zuckerberg & Priscilla Chan’s CZI fund for African Engineers. Zuckerberg’s surprise visit to Lagos in 2016 sent shockwaves across the African tech community, and awakened those unaware of the exploding African tech economy. The Andela-CZI partnership spurned a new era in African entrepreneurship catalyzing billions of dollars in investment interest in African startups, with investments surpassing $1 billion in both 2019 and 2020. Aboyeji has since gone on to found two more startups–Flutterwave and Future Africa–and invested in many impact-focused enterprises. Future Africa returned $3.7M to investors at the end of 2020, experiencing explosive growth across their portfolio in the midst of the pandemic. Aboyeji regularly writes and speaks on the urgency of inclusive African development, and the need for African elites to do more for the plight of the common man. Black Genius is hosted by Lolade Siyonbola, Founder of NOIR Labs, noirpress and NOIR FEST. Lolade is a Gates Scholar and Harambean pursuing a PhD in Sociology at Cambridge University *** Black Geniuses are changing the world, from policy to culture to tech to art. Are you a Black Genius? Send us your story at editor@noirpress.org Join the noirpress movement on Youtube, IG, Twitter and Facebook to see how we are normalizing the Glory of Blackness. For our newsletter curating the best in Black news and films, join our mailing list at noirpress.org.

Brent Maddin talks with Dr. Brooke Stafford-Brizard, Vice President for Research to Practice at the Chan Zuckerberg Initiative, in advance of Building the Next Normal, the January 2021 convening hosted by ASU's Mary Lou Fulton Teachers College, where Brooke will be a featured expert.Comments? Feedback? Ideas? Drop us a line at edworkforce@asu.edu. Follow MLFTC on Twitter at @asueducation and follow Brooke at @StaffordBrizard. Share this episode with #NextEducationWorkforce.1:39: Brooke talks about the importance of measuring a broader set of outcomes in our effort to define “success” for students--outcomes like curiosity, emotional intelligence and flexibility.3:05: Brooke describes the traction she sees in policies connecting mental health and well-being to schools and districts.4:12: Brooke makes the connection between a broader set of outcomes and educational equity: “When we are focusing on equity within the learning environment, thinking about students as whole individuals is critical.”5:26: Brooke describes changes she would like to see in teacher prep and leadership prep programs and describes how we might know whether a teacher's role is sustainable.7:40: Brooke proposes where we might go to learn more about the identity development of rookie teachers, including Black Teacher Collaborative and PilotEd.8:10: Brooke defines what she sees as the purpose of schooling and describes the framework she developed, Building Blocks for Learning.11:33: Brooke suggests that a team approach to supporting students may offer opportunities for students to connect authentically with educators and describes a partnership CZI has with Nez Perce and the Idaho State Department of Education.12:35: Brooke recommends reading fiction in order to help us develop empathy before they join her at Building the Next Normal, the January 2021 convening hosted by ASU's Mary Lou Fulton Teachers College. 

Bringing you Marc Malandro, Vice President of Operations for Science at the Chan Zuckerberg Initiative (CZI). Many of you might remember Marc leading Pitt's Innovation Institute, but today he will give you key details of CZI and how it leverages technology, community-driven solutions and collaboration to accelerate progress in education, justice/opportunity and science. CZI is using technology to help solve some of our toughest challenges — from preventing and eradicating disease, to improving learning experiences for kids, to reforming the criminal justice system. Founded by Priscilla Chan and Mark Zuckerberg in 2015, CZI’s mission is to build a more inclusive, just, and healthy future for everyone.

Leading Teams to Online Fundraising Overnight Interview with Megan Anhalt Megan Anhalt is the Chief Strategy Officer and COO of Whole Whale. She has over 10 years of experience leading purpose-driven projects to help nonprofits, foundations, and companies create social impact. As a Strategy Director and Senior Strategist for Purpose, Megan drove several campaigns to address some of the world's biggest challenges, including supporting the rights of low wage workers, fighting Parkinson's disease, building a better food system, and improving jobs in America today. Before joining the team at Whole Whale, Megan led digital communications for the Chan Zuckerberg Initiative, managing web, Facebook, and overall digital strategy for Priscilla Chan and the Zuck himself under CZI's philanthropic banner. Leaders looking to build up their digital capacity, especially in fundraising need to know the right people to bring on and train. Organizations are moving all of their work online overnight and there are different skills required. Who should you be hiring? How can you train existing people? How do we measure the success of online fundraising from the beginning? How does increased online fundraising work with existing efforts? Learn more about your ad choices. Visit megaphone.fm/adchoices

Cette année 2020 a décidément un arrière-goût de fin du monde et d’apocalypse. Alors que nous continuons à vivre un quotidien encore fortement modifié par un virus, un autre phénomène se répand : celui de la lutte contre les violences raciales, en rebond à la mort emblématique de Georges Floyd, causée par des policiers dans des conditions particulièrement choquantes. Nous faisons le tour dans cet épisode des réactions de quelques acteurs américains clés dans le monde des réseaux sociaux. Réagissez à l’émission en commentaires sur techcafe.frSoutenez Tech Café sur PatreonDiscutez avec nous et entre vous sur le groupe Telegram   Réactions BlackLivesMatter Facebook, Reddit, Microsoft, Snap, jeu vidéo, des réactions inédites...Les experts : le CZI trouve Facebook coupable, une prochaine remise en question ?Facebook vire des suprémacistes chasse le boogaloo. Premier procès contre le décret “anti biais” IBM arrête la reconnaissance faciale. Et Clearview sinon ?Pour vous protéger, Signal fait des photos floues. So 2020 C’est chaud : Motorola entre en Fusion, un Honor avec un thermomètre.IP man : Huawei fait des stocks de guerre en préparant le futur du réseau.Des “covidbit” à Singapour ? Ca dynamisera le secteur. Ça ne laisse pas indifférent. Vivement le CES 2021, avec de vrais postillons et de la vraie sueur de geek. Jeux vidéo La taille compte : Sega lance les Game Gear Micro. Avec une loupe.Sega évoque peu clairement un projet Fog indistinct.Nouveau look, nouvelle vie, Alyx se fait modder en PT.Quand on veut, on peut. Mais c’est pas pour ça qu’on doit.Ca déchire : la simulation de viande qui donne l’eau à la bouche. En vrac Google+ Pro est arrivé : c’est Google Currents.Nest AwareVous pouvez transférer vos photos Facebook. Après si vous voulez rester...Arte Gaia X : le projet Franco-Allemand de Cloud Européen.Pas brillant : les satellites de Starlink essayent de se faire discrets.Crash Landing pour le Flyer de Kitty Hawk, Larry tourne la page.Double aveugle : IBM propose le chiffrement homomorphe pour Apple.Apple joue la carte de l’open-source pour que tout le monde avance dans le même sens dans le monde merveilleux des mots de passe sécurisés Participants :  Guillaume PoggiaspallaPrésenté par Guillaume Vendé

On this episode of Uncharted Territory, we interview Ruby Bolaria Shifrin, Director of Housing Affordability at the Chan Zuckerberg Initiative. Ruby outlines how COVID-19 is an opportunity for philanthropists to change their risk-appetite and pursue bigger upstream impact. Ruby also shares practical steps for ways foundations can get serious about gender equality and staff diversity.Chan Zuckerberg Initiative is a pioneering 21st-century foundation, and Ruby reveals how they're being the risk-embracing capital that can test new ideas and why most of the people at CZI do not have a background in philanthropyIn this episode, the following articles are cited:As women take over male-dominated fields, pay dropsWhat is holden women back from equal pay?92 percent of foundation presidents and 83 percent of full-time staff members are whiteLess than 8% of philanthropic support goes towards investing in communities of colorThe NFL's Rooney Rule

On this episode of Uncharted Territory, we interview Ruby Bolaria Shifrin, Director of Housing Affordability at the Chan Zuckerberg Initiative. Ruby outlines how COVID-19 is an opportunity for philanthropists to change their risk-appetite and pursue bigger upstream impact. Ruby also shares practical steps for ways foundations can get serious about gender equality and staff diversity.Chan Zuckerberg Initiative is a pioneering 21st-century foundation, and Ruby reveals how they're being the risk-embracing capital that can test new ideas and why most of the people at CZI do not have a background in philanthropyIn this episode, the following articles are cited:As women take over male-dominated fields, pay dropsWhat is holden women back from equal pay?92 percent of foundation presidents and 83 percent of full-time staff members are whiteLess than 8% of philanthropic support goes towards investing in communities of colorThe NFL's Rooney Rule

On this episode of Uncharted Territory, we interview Ruby Bolaria Shifrin, Director of Housing Affordability at the Chan Zuckerberg Initiative. Ruby outlines how COVID-19 is an opportunity for philanthropists to change their risk-appetite and pursue bigger upstream impact. Ruby also shares practical steps for ways foundations can get serious about gender equality and staff diversity.Chan Zuckerberg Initiative is a pioneering 21st-century foundation, and Ruby reveals how they're being the risk-embracing capital that can test new ideas and why most of the people at CZI do not have a background in philanthropyIn this episode, the following articles are cited:As women take over male-dominated fields, pay dropsWhat is holden women back from equal pay?92 percent of foundation presidents and 83 percent of full-time staff members are whiteLess than 8% of philanthropic support goes towards investing in communities of colorThe NFL's Rooney Rule

Not surprisingly, COVID-19 has taken over the news section, but still as it all relates to AI and machine learning. Andy and Dave discuss the COVID-19 Open Research Data Set, a free resource of over 29,000 scholarly articles on the coronavirus family, made available for the Allen Institute, CSET, CZI, Microsoft Research, NIH, and the White House OSTP. In similar news, over 100 organizations have signed a “wellcome statement” to make COVID-19 research and data open for access. The New England Complex Systems Institute provides a host of pandemic resources online. The CDC is using machine learning to forecast COVID-19 (adapting its efforts in forecasting influenza outbreaks). And Anodot launches a public machine learning-driven service to track COVID-19. In research, somehow not COVID-19 related, Google Brain and Google Research demonstrate Auto-ML Zero, which discovers complete machine learning algorithms by using basic mathematical functions as building blocks. The report of the week comes from Complex Multilayer Networks Lab along with Harvard, which provides a COVID-19 Infodemics Observatory, processing more than 100M tweets to quantify various sentiments as well as reliability of information from around the globe (with Singapore topping the list for most reliable information). David Barber provides Bayesian Reasoning and Machine Learning for free. And the Bipartisan Commission on Biodefense and Max Brooks provide Germ Warfare: a Very Graphic History (published in 2019). Click here to visit our website and explore the links mentioned in the episode.   

Nun ist es fast geschafft, der Advent ist das vorbei und Störnachten ist auf der Zielgeraden. Heute treffen wir uns mit allen Hörern und jungen Leuten, die noch das Jahr zusammen ausklingen lassen wollen. Herzliche Einladung um 16:00 Uhr ins CZI, Dorfstr 20, 25524 Itzehoe

Matt and Courtney interview Dr. Brooke Stafford-Brizard, a keynote speaker at the Aurora Institute Symposium 2019. She talks about mental health and the future of whole child education.From inacol.org: Dr. Brooke Stafford-Brizard is the Director of Whole Child Development at the Chan Zuckerberg Initiative, where she leads work to support a comprehensive, Whole Child approach to learning and development. Before joining CZI, Dr. Stafford-Brizard worked as an independent consultant supporting the integration of cognitive and social-emotional development into school districts and charter management organizations through a connection between research, policy, and practice. As a Senior Advisor with Turnaround for Children, Dr. Stafford-Brizard authored The Building Blocks for Learning, a nationally recognized developmental framework supporting comprehensive student development. She began her career as a teacher with Teach for America at an intermediate school in the Bronx and later co-founded the Young Women’s College Prep Charter School in Rochester, NY. Stafford-Brizard is a Pahara-Aspen Education Fellow and a member of the Aspen Institute’s Global Leadership Network.

Matt and Courtney interview Dr. Brooke Stafford-Brizard, a keynote speaker at the Aurora Institute Symposium 2019. She talks about mental health and the future of whole child education.From inacol.org: Dr. Brooke Stafford-Brizard is the Director of Whole Child Development at the Chan Zuckerberg Initiative, where she leads work to support a comprehensive, Whole Child approach to learning and development. Before joining CZI, Dr. Stafford-Brizard worked as an independent consultant supporting the integration of cognitive and social-emotional development into school districts and charter management organizations through a connection between research, policy, and practice. As a Senior Advisor with Turnaround for Children, Dr. Stafford-Brizard authored The Building Blocks for Learning, a nationally recognized developmental framework supporting comprehensive student development. She began her career as a teacher with Teach for America at an intermediate school in the Bronx and later co-founded the Young Women’s College Prep Charter School in Rochester, NY. Stafford-Brizard is a Pahara-Aspen Education Fellow and a member of the Aspen Institute’s Global Leadership Network.

The Story Collider is delighted to bring you an extra BONUS episode this week -- thanks to the Chan Zuckerberg Initiative, a new kind of philanthropy that’s leveraging technology to help solve some of the world’s toughest challenges. Both of the stories featured in this episode were recorded a very special show we produced in collaboration with CZI last June in Aspen, about rare medical conditions and the importance of leveraging the power of patients to accelerate research and drive progress. Part 1: Luke Rosen signs his daughter up for a research study to find out what's causing her seizures and ends up having to fight to find the answers. Part 2: After stay-at-home mom Tracy Dixon-Salazar's daughter is diagnosed with epilepsy, she enrolls in school in order to decipher what is happening. Luke Rosen and Sally Jackson founded KIF1A.ORG in 2016 following their daughter Susannah’s KIF1A diagnosis. Luke has extensive experience in rare disease stakeholder engagement, advocacy and research initiatives. Recognized by Global Genes as a 2018 RARE Champion of Hope Honoree, Luke often speaks at international events about innovation in therapeutic development, and about his family’s rare disease journey. Luke’s mission is to accelerate biotech innovation and forge efficient collaborations within the scientific and patient communities, resulting in discovery of treatment for children like Susannah. He relentlessly works to empower families affected by rare genetic diseases to play an active role in discovery, from pre-clinical research through clinical trial readiness and regulatory approval. Dr. Tracy Dixon-Salazar is a neuroscientist, geneticist, and, patient advocate. Her desire to get her Ph.D. was inspired by her daughter who developed Lennox-Gastaut Syndrome (LGS) at the age of 2. She did her Ph.D. and post-doctoral work at UC, San Diego where she studied the mechanisms of brain development and synaptic plasticity, identified genetic causes of rare disorders in children, and researched precision therapeutics in stem cell and animal models of pediatric disease. During her research tenure, and after 16 years of watching daily, unrelenting seizures in her child, she uncovered the driver of her daughter’s illness and identified a novel precision therapy that improved her child's life. Dr. Dixon-Salazar is an accomplished scientist, proven thought leader, highly sought-after speaker, and staunch advocate for genomic medicine, patient-centric research, and patient engagement.  Learn more about your ad choices. Visit megaphone.fm/adchoices

Our first episode of the year features Jim Shelton and Rebecca Winthrop to bring you a macro-level view of education and access. We also find out the underlying challenges that may give us clues to answer the question: how do we take the luck out of education? This two-part episode begins with some of the different facets that contribute to inequality and the second part will look at what we can do to make sure that every young person, regardless of their background, is able to pursue their education. Jim Shelton is the former Head of the Chan Zuckerberg Initiative’s Education division, and also the former Deputy Secretary of the United States Department of Education. You can follow Jim on Twitter @JIMSEDU, and find out more about CZI here: chanzuckerberg.com/ Dr Rebecca Winthrop is the Senior Fellow and Director of the Center for Universal Education at the Brookings Institution. You can follow Rebecca on Twitter @RebeccaWinthrop, and find out more about Brookings here: www.brookings.edu/center/center-fo…ersal-education/ This episode is narrated by WISE Words co-producer, Vesta Gheibi. #WISEPod

Our first episode of the year features Jim Shelton and Rebecca Winthrop to bring you a macro-level view of education and access. We also find out the underlying challenges that may give us clues to answer the question: how do we take the luck out of education? This two-part episode begins with some of the different facets that contribute to inequality and the second part will look at what we can do to make sure that every young person, regardless of their background, is able to pursue their education. Jim Shelton is the former Head of the Chan Zuckerberg Initiative’s Education division, and also the former Deputy Secretary of the United States Department of Education. You can follow Jim on Twitter @JIMSEDU, and find out more about CZI here: chanzuckerberg.com/ Dr Rebecca Winthrop is the Senior Fellow and Director of the Center for Universal Education at the Brookings Institution. You can follow Rebecca on Twitter @RebeccaWinthrop, and find out more about Brookings here: www.brookings.edu/center/center-fo…ersal-education/ This episode is narrated by WISE Words co-producer, Vesta Gheibi. #WISEPod

Mike and Dan welcome two great guests, Bror Saxberg and Glenn Whitman, to discuss the Chan Zuckerberg Initiative, The Center for Transformative Teaching and Learning, neuroscience and learning, and how a holistic approach to education applies to teaching and teacher development. Phew! Bror, Vice President, Learning Science at CZI, discusses the mission of the organization and how it recently invested in CTTL. Glenn describes the work that's been done on a local level at the St. Andrew's Episcopal School in Maryland and how that work is being scaled across the US and globally through CZI. Can training teachers on how the brain works make them more effective in the classroom? We talk often about teaching the whole student, but can we miss out on reaching the whole teacher? CTTL has done some great work in the field and have partnered with CZI to build NeuroTeach, which is set to launch broadly in January. Tune in for a wide-ranging discussion on neuroscience, learning engineering, growth mindset, microlearninf, and much more. We may even debunk a few neuromyths before we’re done. Enjoy!

经常看到人们在激烈地讨论奶茶妹妹的感情生活，也有不少人疯狂求邓文迪出书，毕竟曾嫁给默多克，前阵子又和小奶狗恋爱，这姐姐的人生颇为传奇。但有一位大佬的妻子，似乎从没受到太多的关注。Facebook创始人扎克伯格，有“第二盖茨”之称的社交网络领跑者，在他28岁那年，娶了相爱九年的美籍华裔女孩，普莉希拉 •陈为妻。或许是因为小扎的年少有为，毕竟他20岁就建立了facebook，还曾多次被评选为全球最年轻亿万富豪。也或许是因为小扎发糖过甜引起不（ji）适（du），比如在哈佛演讲也不忘表白妻子：“我在哈佛最美好的回忆，是我遇见了普莉希拉。”相当一部分人对普莉希拉颇有微词，说她“其貌不扬，太过普通，她能嫁给扎克伯格，怕是上辈子拯救了国家”。但其实，如果对普莉希拉稍作了解，人们就会发现，这绝对不是一个王子爱上灰姑娘的故事，普莉希拉，本身就是位光芒万丈的公主。普莉希拉的父亲是旅居越南的华裔，上世纪70年代，他和妻子一起来到了美国马萨诸塞州的昆西，一个成为服务生，一个成为会计，起早贪黑地谋生活。后来，他们有了孩子，普莉希拉是姐妹中最先出生的，父母无暇照顾，就只能让爷爷奶奶陪伴着她。大概因为父母忙着养家，而她又是家里的老大，普莉希拉从小就很独立，并且承担起照料这个家的责任。而对于父母来说，即使为了生计连陪伴孩子都无法做到，即使他们自己受教育程度有限，但他们的理念很清晰：一定要让孩子们接受教育。于是，当普莉希拉对妈妈说“学校老师让我去学SATS”时，妈妈的回答很酷：“虽然不知道这是什么，但你需要我送你去吗？”在普莉希拉的家人眼里，教育可以帮助他们的孩子通往更好的未来。在家人的全力支持下，普莉希拉也十分争气，她在中学就被同学们称为“班级天才”，最终以优异的成绩进入哈佛大学，成为了家里第一个上大学的人。尽管对于普莉西亚来说，哈佛意味着更多的机遇，但这同时也意味着更多的挑战和压力。提到这段经历时，她甚至掉下了眼泪。更优秀的人，激烈的竞争，难以融入的环境，使她认为自己是个失败者，她甚至填写了转学文书想要离开哈佛。“聪明是我唯一的优势，但是在哈佛比我聪明的太多了。”决定离开后，普莉希拉想着，走之前总要做些什么，于是她带领了一个课外小组，加入了一个低收入者安居项目，去做志愿者，辅导孩子们做作业，为提高他们的受教育条件努力。而在这里的一个小女孩，使她彻底改变了转学的决定。有一天，一名学校辅导员找到她，说有一名10岁的女孩，好几天没有去上学了。普莉希拉和其他志愿者们开始寻找，幸运的是，她在安居房附近的操场上找到了这个小女孩。但让普莉西亚难过的是，小女孩没去学校的原因是两颗门牙被打断，她不敢见人，也就不敢去上学。那一刻，普莉希拉心中充满痛苦和愤怒，脑海里涌现出很多问题和念头：“她的牙齿会感染吗？”“我是不是本可以做些什么？这伤害是不是本来可以不发生？”“我能做些什么来防止类似的情况？”“我必须留下来，必须有所作为，我要帮助他们，打开新世界的大门。”这件事情促使普莉希拉自省，她认为自己不该困于个人痛苦，自己应该看到更大的格局。因此，她没有转学，而是选择进入哈佛医学院，去拓展自己的技能，以帮助更多的小孩茁壮成长。这一次不再仅是保护家人，她想要扛起更大更广的责任。在哈佛，普莉希拉不仅拓展了自我认知，明白了自己的人生方向，她也在这里，遇到了自己的爱情。有趣的是，她第一次遇见扎克伯格，是在哈佛的宿舍楼里，那时候小扎正因为创建一个校园网站陷入争议，面临退学的危险。所以他是这么搭讪的：“我们明天就约会吧，因为我可能很快就要被学校开除了。”高，实在是高。等到他们真的约会时，小扎同学开始了强行撩妹：“和你在一起真好，我们一起再去看场电影？虽然我还有个期中考试要准备，但是我更想和你在一起。”小扎这话一出口，整段垮掉。因为在学霸普莉希拉看来，连学习都不能好好去做，以后能做啥呢？于是普莉希拉拒绝了，并告诉他回去好好看书。小扎内心戏演了几百回合：她都不愿意和我去看电影，应该是对我没意思吧。但其实，普莉希拉只是希望，扎克伯格可以严格要求自己。这样的督促，从学生生涯，一直延续到今天，她在“爱人”和“伙伴”的身份间任意切换，意见该提，支持该给，而一路的困难，也该一起度过。毕业后，即便小扎已经开拓出社交霸业，普莉希拉却没有选择进入Facebook谋职，而是坚持着自己的梦想，她先是成为了一名教师，两年后，进入世界著名的生命科学及医学中心，加利福尼亚大学旧金山分校继续深造，最终，她成为一名牙医。小扎情话上线：我太为你骄傲了，陈医生。而她也影响着扎克伯格，投身于慈善。因为她热心教育、关注儿童成长，于是扎克伯格给学校大量捐钱。因为她成为儿科医生，在家里经常会谈论起病人难以获得器官捐献的现状，于是扎克伯格开始在Facebook上推广器官捐献项目，第一天就有大约10万人注册。2015年，他们有了女儿，在一封写给他们新生女儿的公开信中，她与丈夫宣布捐出在Facebook持有的99%股份，成立一个旨在参与慈善及政治行动的慈善机构（CZI），致力于预防、治疗疾病以及推广平等教育等 。当初那个看到10岁女孩心痛不已的姑娘，如今已经实现了那时的决心：“我要变得更强大，来保护他们。”或许就像很多人说的那样，普莉希拉真的很平凡，她没有了不起的家世和曲折的故事，没有华丽的包装和噱头，她只是作为一名独立、坚定、温柔的女士，为社会更加公平而努力前行。如今，世人会以普莉希拉•陈而记住她，绝不仅仅是“扎克伯格的妻子”。

经常看到人们在激烈地讨论奶茶妹妹的感情生活，也有不少人疯狂求邓文迪出书，毕竟曾嫁给默多克，前阵子又和小奶狗恋爱，这姐姐的人生颇为传奇。但有一位大佬的妻子，似乎从没受到太多的关注。Facebook创始人扎克伯格，有“第二盖茨”之称的社交网络领跑者，在他28岁那年，娶了相爱九年的美籍华裔女孩，普莉希拉 •陈为妻。或许是因为小扎的年少有为，毕竟他20岁就建立了facebook，还曾多次被评选为全球最年轻亿万富豪。也或许是因为小扎发糖过甜引起不（ji）适（du），比如在哈佛演讲也不忘表白妻子：“我在哈佛最美好的回忆，是我遇见了普莉希拉。”相当一部分人对普莉希拉颇有微词，说她“其貌不扬，太过普通，她能嫁给扎克伯格，怕是上辈子拯救了国家”。但其实，如果对普莉希拉稍作了解，人们就会发现，这绝对不是一个王子爱上灰姑娘的故事，普莉希拉，本身就是位光芒万丈的公主。普莉希拉的父亲是旅居越南的华裔，上世纪70年代，他和妻子一起来到了美国马萨诸塞州的昆西，一个成为服务生，一个成为会计，起早贪黑地谋生活。后来，他们有了孩子，普莉希拉是姐妹中最先出生的，父母无暇照顾，就只能让爷爷奶奶陪伴着她。大概因为父母忙着养家，而她又是家里的老大，普莉希拉从小就很独立，并且承担起照料这个家的责任。而对于父母来说，即使为了生计连陪伴孩子都无法做到，即使他们自己受教育程度有限，但他们的理念很清晰：一定要让孩子们接受教育。于是，当普莉希拉对妈妈说“学校老师让我去学SATS”时，妈妈的回答很酷：“虽然不知道这是什么，但你需要我送你去吗？”在普莉希拉的家人眼里，教育可以帮助他们的孩子通往更好的未来。在家人的全力支持下，普莉希拉也十分争气，她在中学就被同学们称为“班级天才”，最终以优异的成绩进入哈佛大学，成为了家里第一个上大学的人。尽管对于普莉西亚来说，哈佛意味着更多的机遇，但这同时也意味着更多的挑战和压力。提到这段经历时，她甚至掉下了眼泪。更优秀的人，激烈的竞争，难以融入的环境，使她认为自己是个失败者，她甚至填写了转学文书想要离开哈佛。“聪明是我唯一的优势，但是在哈佛比我聪明的太多了。”决定离开后，普莉希拉想着，走之前总要做些什么，于是她带领了一个课外小组，加入了一个低收入者安居项目，去做志愿者，辅导孩子们做作业，为提高他们的受教育条件努力。而在这里的一个小女孩，使她彻底改变了转学的决定。有一天，一名学校辅导员找到她，说有一名10岁的女孩，好几天没有去上学了。普莉希拉和其他志愿者们开始寻找，幸运的是，她在安居房附近的操场上找到了这个小女孩。但让普莉西亚难过的是，小女孩没去学校的原因是两颗门牙被打断，她不敢见人，也就不敢去上学。那一刻，普莉希拉心中充满痛苦和愤怒，脑海里涌现出很多问题和念头：“她的牙齿会感染吗？”“我是不是本可以做些什么？这伤害是不是本来可以不发生？”“我能做些什么来防止类似的情况？”“我必须留下来，必须有所作为，我要帮助他们，打开新世界的大门。”这件事情促使普莉希拉自省，她认为自己不该困于个人痛苦，自己应该看到更大的格局。因此，她没有转学，而是选择进入哈佛医学院，去拓展自己的技能，以帮助更多的小孩茁壮成长。这一次不再仅是保护家人，她想要扛起更大更广的责任。在哈佛，普莉希拉不仅拓展了自我认知，明白了自己的人生方向，她也在这里，遇到了自己的爱情。有趣的是，她第一次遇见扎克伯格，是在哈佛的宿舍楼里，那时候小扎正因为创建一个校园网站陷入争议，面临退学的危险。所以他是这么搭讪的：“我们明天就约会吧，因为我可能很快就要被学校开除了。”高，实在是高。等到他们真的约会时，小扎同学开始了强行撩妹：“和你在一起真好，我们一起再去看场电影？虽然我还有个期中考试要准备，但是我更想和你在一起。”小扎这话一出口，整段垮掉。因为在学霸普莉希拉看来，连学习都不能好好去做，以后能做啥呢？于是普莉希拉拒绝了，并告诉他回去好好看书。小扎内心戏演了几百回合：她都不愿意和我去看电影，应该是对我没意思吧。但其实，普莉希拉只是希望，扎克伯格可以严格要求自己。这样的督促，从学生生涯，一直延续到今天，她在“爱人”和“伙伴”的身份间任意切换，意见该提，支持该给，而一路的困难，也该一起度过。毕业后，即便小扎已经开拓出社交霸业，普莉希拉却没有选择进入Facebook谋职，而是坚持着自己的梦想，她先是成为了一名教师，两年后，进入世界著名的生命科学及医学中心，加利福尼亚大学旧金山分校继续深造，最终，她成为一名牙医。小扎情话上线：我太为你骄傲了，陈医生。而她也影响着扎克伯格，投身于慈善。因为她热心教育、关注儿童成长，于是扎克伯格给学校大量捐钱。因为她成为儿科医生，在家里经常会谈论起病人难以获得器官捐献的现状，于是扎克伯格开始在Facebook上推广器官捐献项目，第一天就有大约10万人注册。2015年，他们有了女儿，在一封写给他们新生女儿的公开信中，她与丈夫宣布捐出在Facebook持有的99%股份，成立一个旨在参与慈善及政治行动的慈善机构（CZI），致力于预防、治疗疾病以及推广平等教育等 。当初那个看到10岁女孩心痛不已的姑娘，如今已经实现了那时的决心：“我要变得更强大，来保护他们。”或许就像很多人说的那样，普莉希拉真的很平凡，她没有了不起的家世和曲折的故事，没有华丽的包装和噱头，她只是作为一名独立、坚定、温柔的女士，为社会更加公平而努力前行。如今，世人会以普莉希拉•陈而记住她，绝不仅仅是“扎克伯格的妻子”。

This week on the podcast we talk with Megan Anhalt, a digital campaign expert who has worked with DoSomething.org, CZI, and Purpose. Megan shares her research and training around the elements of storytelling for campaigns and what it takes to "go viral". We explore how nonprofits can and should take advantage of 'crisitunities', moments when the news and world events create an opportunity for a message.

Episode 16: Charlotte Weaver So glad you found us! Pull up a chair or beach towel and join us for my conversation with Charlotte Weaver about her transitions along the pathways of life. Dr. Janet K. Lee   ORIGINAL MUSIC by CONNOR REESE