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In this episode, I chatted with Dr. Kaitlyn Sadtler, who is pushing the boundaries of biomedical science. Co-hosted with HHMI Gilliam Fellow and ChemE PhD Candidate Sydney Floryanzia, we talk about their groundbreaking research, the twists and turns of their scientific journeys, and the power of collaboration in tackling big challenges.More on Dr. Sadtler, per the NIBIB:Kaitlyn Sadtler, Ph.D. joined NIBIB as an Earl Stadtman Tenure-Track Investigator and Chief of the Section for Immunoengineering in 2019. Prior to her arrival to the NIH, she completed a postdoctoral fellowship at the Massachusetts Institute of Technology with Daniel Anderson, Ph.D. and Robert Langer, Ph.D., focusing on the molecular mechanisms of medical device fibrosis. During her time at MIT, Dr. Sadtler was awarded an NRSA Ruth L Kirschstein Postdoctoral Fellowship, was listed on BioSpace's 10 Life Science Innovators Under 40 To Watch and StemCell Tech's Six Immunologists and Science Communicators to Follow. In 2018, she was named a TED Fellow and delivered a TED talk which was listed as one of the 25 most viewed talks in 2018. She was also elected to the 2019 Forbes 30 Under 30 List in Science, selected as a 2020 TEDMED Research Scholar, and received multiple other awards. Dr. Sadtler received her Ph.D. from the Johns Hopkins University School of Medicine where her thesis research was published in Science magazine, Nature Methods, and others. She was recently featured in the Johns Hopkins Medicine Magazine as an alumna of note. Dr. Sadtler completed her bachelor's degree summa cum laude at the University of Maryland Baltimore County, followed by a postbaccalaureate IRTA at the Laboratory of Cellular and Molecular Immunology at NIAID.
Renzo Huber is a staff scientist at NIH. We talk about his work on layer-fMRI: what it is, how Renzo got into it, how to do it, when it makes sense to do it, what the future holds, and much more.Support the show: https://geni.us/bjks-patreonTimestamps0:00:00: How Renzo got into high-resolution fMRI0:11:28: The difference between 3T and 7T fMRI0:22:46: Is a bigger fMRI scanner always better?0:33:35: Layer-fMRI0:56:28: For what types of research is layer-fMRI most useful?1:02:35: How to do layer-fMRI and make it reproducible1:19:21: The future of layer-fMRI1:27:02: A book or paper more people should read1:30:37: Something Renzo wishes he'd learnt sooner1:33:11: Advice for PhD students/postdocsPodcast linksWebsite: https://geni.us/bjks-podTwitter: https://geni.us/bjks-pod-twtRenzo's linksWebsite: https://geni.us/huber-webGoogle Scholar: https://geni.us/huber-scholarTwitter: https://geni.us/huber-twtBen's linksWebsite: https://geni.us/bjks-webGoogle Scholar: https://geni.us/bjks-scholarTwitter: https://geni.us/bjks-twtReferences and links mentionedEpisode with Peter Bandettini: https://geni.us/bjks-bandettiniEpisode with Emily Finn: https://geni.us/bjks-finnRenzo's blog about layer fMRI: https://layerfmri.com/YouTube channel on layer fMRI: https://www.youtube.com/@layerfmri/Bastos, ... & Friston (2012). Canonical microcircuits for predictive coding. Neuron.Bollmann & Barth (2021). New acquisition techniques and their prospects for the achievable resolution of fMRI. Progress in Neurobiology.Boulant, ... & Le Bihan (2024). In vivo imaging of the human brain with the Iseult 11.7-T MRI scanner. Nature Methods.Finn, ... & Bandettini (2019). Layer-dependent activity in human prefrontal cortex during working memory. Nature Neuroscience.Feynman (1985). "Surely you're joking, Mr. Feynman!": adventures of a curious character.Haarsma, Kok & Browning (2022). The promise of layer-specific neuroimaging for testing predictive coding theories of psychosis. Schizophrenia Research.Huber, ... & Bandettini (2017). High-resolution CBV-fMRI allows mapping of laminar activity and connectivity of cortical input and output in human M1. Neuron.Huber, ... & Möller (2019). Non-BOLD contrast for laminar fMRI in humans: CBF, CBV, and CMRO2. Neuroimage.Huber, ... & Bandettini (2020). Sub-millimeter fMRI reveals multiple topographical digit representations that form action maps in human motor cortex. Neuroimage.Huber, ... & Kronbichler (2023). Evaluating the capabilities and challenges of layer-fMRI VASO at 3T. Aperture Neuro.Huber, ... & Horovitz (2023). Laminar VASO fMRI in focal hand dystonia patients. Dystonia.Persichetti, ... & Martin (2020). Layer-specific contributions to imagined and executed hand movements in human primary motor cortex. Current Biology.Polimeni, ... & Wald (2010). Laminar analysis of 7 T BOLD using an imposed spatial activation pattern in human V1. Neuroimage.
Tune in to hear all about Pixelgen Technologies - creators of a novel technology for doing single-cell spatial proteomics. We chat about how this fascinating technology works, what you can do with the data and why they chose to develop their analysis suite as an open-source nf-core pipeline. Links: Software: nf-core/pixelator pipeline Pixelator Python package Science: Nature Methods publication: “Molecular pixelation: spatial proteomics of single cells by sequencing” Presentations: Nextflow Summit 2022 talk: “Pixelgen Technologies ❤︎ Nextflow” Nextflow Summit 2024 Boston talk: “Nextflow allows Pixelgen innovation engine to reach the market quicker” Nextflow Summit 2024 Barcelona Pixelgen: Pixelgen Technologies homepage @PixelgenTech on twitter / X and LinkedIn BioLizard: BioLizard homepage @BioLizard_nv on twitter / X and LinkedIn Chapters: Start (00:00) Welcome (00:09) Introductions (00:50) Intro to Pixelgen Technologies (01:41) Lab methods (03:08) Nature Methods publication (06:15) Data visualisation (09:35) Working with single cell data (12:29) Cell interactions (15:06) Why Pixelgen chose open source (16:05) Pixelator Python package (20:10) Building within nf-core (21:40) Florian - Biolizard (23:01) Pipeline overview (25:19) Using nf-core from a commercial setting (26:50) Coming out of stealth (28:53) Extending Pixelator (32:24) Dealing with customers (34:58) Looking to the future (39:38) Interactive analysis (41:32) Advice for others (43:12) Pixelgen at the Nextflow Summit (45:16)
David Dalrymple, with a background from MIT and Harvard, is known for his study on Caenorhabditis elegans' nervous system, featured in Nature Methods. At Oxford University, his work spans neuroinformatics, machine learning, and software engineering. He is also a co-inventor of Filecoin.Key HighlightsA 10-year plan for brain uploading, dismissing certain techniques like neural dust, while highlighting expansion microscopy and immunofluorescence as promising.The use of AI for parameter estimation from destructive imaging, with a focus on automation for scalability.Validation techniques involving human brain slices and the application of advanced imaging and experimental methods.The challenges of dense brain data transfer and the potential solutions through mapping algorithms and axon tracing.Dive deeper into the session: Full SummaryAbout Foresight InstituteForesight Institute is a research organization and non-profit that supports the beneficial development of high-impact technologies. Since our founding in 1987 on a vision of guiding powerful technologies, we have continued to evolve into a many-armed organization that focuses on several fields of science and technology that are too ambitious for legacy institutions to support.Allison DuettmannThe President and CEO of Foresight Institute, Allison Duettmann directs the Intelligent Cooperation, Molecular Machines, Biotech & Health Extension, Neurotech, and Space Programs, alongside Fellowships, Prizes, and Tech Trees. She has also been pivotal in co-initiating the Longevity Prize, pioneering initiatives like Existentialhope.com, and contributing to notable works like "Superintelligence: Coordination & Strategy" and "Gaming the Future".Get Involved with Foresight:Apply: Virtual Salons & in-person WorkshopsDonate: Support Our Work – If you enjoy what we do, please consider this, as we are entirely funded by your donations!Follow Us: Twitter | Facebook | LinkedInNote: Explore every word spoken on this podcast through Fathom.fm, an innovative podcast search engine. Hosted on Acast. See acast.com/privacy for more information.
Labs and a lab's team members often speak many languages. Science is international. But in a lab environment languages can set people apart. I wrote a story about lab languages for Nature Methods here: https://rdcu.be/doPnv There's a blog post here: https://cellmolbiocommunity.springernature.com/posts/podcast-lab-languages . And here is more from that story. It's a conversation with Dr. Denis Wirtz, a cancer researcher at Johns Hopkins University and Johns Hopkins School of Medicine and vice-provost for research at Hopkins. (Music: Better by Dizzy, Art J. Jackson)
Eric Topol (00:00):Hello, this is Eric Topol, and I'm thrilled to have a chance to have a conversation with Magdalena Skipper, who is the Editor-in-Chief of Nature. And a historic note. Back in 2018, she became the first woman editor of Nature in its 149 years, and only the eighth editor of all times. Having taken over for Philip Campbell, who had been previously the editor for 22 years, we're going to ask her if she's going to do 22 or more years, but we're going to have a fun conversation because there's so much going on in medical publishing, and I think, you know, that Nature is the number one cited science journal in the world. So, welcome, Magdalena.Magdalena Skipper (00:41):Thank you very much. Real pleasure to be here and chatting with you today, Eric. Thank you.How COVID-19 Affected NatureEric Topol (00:47):Well, you know, we're still, of course, in the pandemic world. It's obviously not as bad as it had been, but there's still things going on with new variants and Long Covid, and it's not, the virus isn't going away. But first thing I wanted to get into was how did Nature handle this frenetic craziness? I mean, it was putting out accelerated publications on almost a daily or weekly basis and putting out like a speed, velocity of the likes that we've not seen. This must have been really trying for the whole crew. What, what do you think?Magdalena Skipper (01:29):It was! And, you know, the first thing I, I think I will recognize two things at the same time. So the first one, as you say, at a time, such as the pandemic, but actually at any point when there is a, a new health emergency that is spreading, especially something as unknown, as new as, as it was the case with SARS-CoV-2. And of course, in the beginning, we really knew nothing about what we were facing if speed is of the essence, but equally what's truly important is of course, the rigor itself. So that combination of needing to publish as quickly as possible, but at the same time as rigorously evaluating the papers as possible, that was actually quite a challenge. And of course, you know, what we sometimes forget when we talk about, well, researchers themselves, but also editors and publishers is of course, as individuals, as human beings.(02:33):They are going through all the trauma, all the constraints associated with various lockdowns concerns about the loved ones, perhaps those ones who are in the care. You know, in many cases of course there would've been the elderly who are individuals would've been concerned by or indeed children, because of course, schools in so many places were. And all the while, while we were dealing with these very human, very ordinary daily preoccupations, we were very focused on the fact that we had a responsibility and a duty to publish papers and evaluate them as quickly as possible. It really was an extraordinary time. And, and you know, one other thing I should emphasize is, of course, it's not just the manuscript editors who evaluate the research, it's the reporters on my team as well who are going out of their the way to find out as much information to report as robustly, find as many sources to, to interview as possible.(03:44):And, and, you know, I also have to mention colleagues who work on production side of nature actually make Naturehappen, be published online on a daily and then of course weekly basis. And literally from one week to the next all our operations had to be performed from home. And it's really remarkable that the issue was not late. We published the issue, just as you know, from as lockdowns came in. And as it happens, the production side of Nature is mainly based in, in London. So most of that team effectively found themselves not being able to go to the office effectively from one day to the next. So it really was an extraordinary time and, and a time that as I said was, was a time of great responsibility. But looking back on it, I'm actually incredibly proud of, of my team, what, what they achievedEric Topol (04:47):Did they hold up? I mean, they hadn't, they didn't get burnout from lack of sleep and lack of everything. Are they still hanging in there?Magdalena Skipper (04:55):So they are hanging in there. You'll be glad to hear. But I think, very importantly, we were there for one another insofar that we could be, of course, we were all at home remotely. We were not meeting, but we had virtual meetings, which were regular of course in as a whole team, but also in, in subgroups as we sub-teams, as we worked together, that human contact in addition to of course, loved ones and families and friends, that human contact in a professional setting was, was really, really necessary. And clearly what I'm describing was affected all of us one way or another. Sometimes there is a tendency not to remember. That also applies to editors, publishers, and of course researchers themselves. I mean, very clearly they were at the forefront of the issue facing the same problems.Nature and Challenge of Generative A.I.Eric Topol (05:57):Well, a new challenge has arisen, not that the pandemic of course has gone away, but now we have this large language models of AI, Generative AI, which you've written editorials at Nature, which, of course, is it human or is it the machine? What do you think about that challenge?Magdalena Skipper (06:19):Well of course, you know, the way I like to think about it is AI, of course, broadly is, has been around for a very long time, a number of decades, right? And steadily over the last several years, we have seen AI emerge as a really powerful and important tool in research right across a number of disciplines. The reason why we are all talking about AI right now, and I really think all of us are talking about AI all the time, is, of course, specifically the emergence of generative AI, the large language models that, that you just mentioned. And they sort of burst onto the scene for all of us really last year in the autumn with chat GPT and GPT-4 and so on. But it's important to remember that, of course, when we talk about AI, there are other models, other approaches, and machine learning in general has been creating quite some revolution in research already.(07:36): You know, probably the best example that will be familiar to many of the listeners was of course Alpha Fold which, you know, Nature published a couple of years ago and, and has been really revolutionized structural biology. But, of course, there are many other examples which are now becoming developing much more rapidly, becoming much more, I would say, commonplace in, in research practice. You know, not just predicting structure from sequencing from sequence. And I say just so flippantly now, of course, it was such and it continues to be such an incredible tool. But of course now we have AI approaches, which actually suggest new protein design, new, new small molecule design. We've had in the last couple of years, we've had identification of new potential antibiotics that are effective against bacterial strains that have otherwise been resistant to any known antibiotics.(08:48):And, and of course, it's not just in biomedicine. Material science--I think it's very helpful, hopeful when it comes to, to AI tools as well. And then, and of course, generative AI indeed helps us in some of these contexts already. But I think your question perhaps was more focused on the publishing, the communication, the sort of output of, of research, which of course is also very important. In some way. The reason why I answered, I began to answer the question the way I did, is because I'm actually very excited about harnessing the power of AI in augmenting research itself. Helping navigate enormous data sets generate hypotheses to be tested finding new ways to advance projects. I think that's a very exciting opportunity. And we're just beginning to see the first applications of it.(10:04):Now, in terms of publishing you referred to some editorials that we wrote about this. And right at the beginning of the year, there was a flurry of excitement associated with the ability of generative AI to indeed generate text. There were some manuscripts which were published in journals that were co-authored by Chat GPT. I I even believe there was an editorial which was co-authored by Chat GPT. So in response to that, we felt very strongly that, that clearly there was a need to, to come out with a, a clear position, just as in doing research, we see AI tools as tools to support writing, but clearly they don't have the ability to fulfill authorship criteria. Clearly, they cannot be authors. Clearly, they must only remain as tools supporting researchers and individuals writing and communicating their research.(11:23):And so we, we wrote a very clear editorial about this, essentially summarizing what I just explained and asking the community to be transparent about how AI tool has been used, just as you would be transparent about your methodology, how you have arrived at the results that you're reporting and, and results that support your conclusions. So for us, it's a relatively simple set of recommendations. As I say, we ask for transparency. We understand it can be a tool that can be used to help write a paper. What we also ask at this stage that generative AI tools are not used to generate figures or images in papers, simply because there are a number of outstanding copyright issues, a number of outstanding privacy issues, they remain unresolved. And for as long as they remain unresolved, we feel it's not an appropriate application of these tools. So that's our editorial position.Eric Topol (12:42):Yeah, no, that's very helpful. I mean, where do you think, if you write a manuscript and then you put it into let's say GPT-4 and say, please edit this, is that okay? Or is that something that, and it's acknowledged that the paper was written by us researchers, but then we had it tweaked by chatbot or is that something that it wouldn't go over too well?Magdalena Skipper (13:10):Well, my preference, and actually what I would hope is that if you were writing this paper and then you felt the need to put it through a chatbot as you just put it, although I find it hard to imagine that you would find no need for that,Eric Topol (13:29):I wouldn't do it. But I know there's people out there that are working on it.Magdalena Skipper (13:32):Yeah, absolutely. But then I would hope that the last pass, the final word, would rest with you as the author. Because, of course, if you are using a tool for whatever it is that you do, you want, at the end of the day to make sure that what that tool has returned is aligned with what you intended that you perform some kind of a sense check. We, of course, all know that although GPT-4 has less of a tendency to hallucinate, so to essentially come up with fabricated sort of statements and, and reality, if you like, it remains an issue. It can remain an issue. And very clearly any, any scientific communication has to be rooted in facts. So, in the scenario that you propose, I would hope that if a researcher felt compelled to run the manuscript through a chatbot, and for example, one consideration may for an individual whose English is not their first language, who feel may feel more comfortable with a sort of support of this kind. But in the end, the final check, the final sign off, if you like, on that manuscript before submission would need to come from the researcher, from the corresponding author, from the writing group. and indeed assistance from a chatbot would need to be disclosed.Eric Topol (15:14):For us. Yeah, I mean, it's really interesting because you can almost foresee the shortcut of having to go get all the references and all the links, you could say, you know, please insert these, but you better check them because they may be fabricated Absolutely. It's going to be really interesting to see how this plays out and the difficulty of detecting what is written by a large language model versus a person.Nature and PreprintsNow another topic that I think is really in play is the preprint world and publishing via preprints. And as you know there's been Michael Eisen and the whole idea of how things would move with his journal eLife. And you will remember when you and I were together at a conference. I organized Future of Genomic Medicine many years ago at the kind of dawn of life science preprints. And some people in the audience sai, “what's a preprint?” Right? Nobody else asks about that now. It's come a long way over this decade. And where do we go with this? Should journals like the top journals in the world like Nature require a paper to be vetted through the pre-print mechanism? Where is this headed, do you think?Magdalena Skipper (16:40):Yeah, it's an excellent question. And, and you know, by the way, I have such wonderful memories from, of that conference. I think this must have been like 11 years ago or something like that. It was a long time ago. And I actually remember presenting this, this vision of a rather radical vision of, of the future of publishing. And here we are in the future as compared to then, and we have moved relatively little by comparison to where we were then. But back to your question. So, you know, the first thing to say is that, of course, just as a reminder, preprints have been around for more than two decades now. And, and of course they initially were really spearheaded and advanced by the physical sciences community. archive itself is, as I say, more than two decades old. So, you know, for us at Nature as a multidisciplinary journal where of course, we've been publishing in the physical sciences since the very beginning of our existence as soon as preprints first emerged in those communities, we realized that we could coexist very harmoniously as a journal peer-review based journal with preprints.(17:59):So when initially biological sciences community embraced them and bioRxiv was established, and then of course, many other archives and then subsequently actually really spearheaded by Covid, the medical and clinical community began to embrace preprints. in many ways, for us, that was nothing new. It was just an extension of something that we worked with before. Although our own our own policies have evolved. So, for example, during the pandemic we actually mandated deposition of papers that were submitted to us that were Covid related. We mandated the deposition in a preprint server. The authors had the choice which server they deposited, but we wanted those manuscripts to be available to the community for the scrutiny as soon as they were finalized, as soon as they were actually written. So while we were reviewing them again as quickly as rigorously, but as quickly as possible, the preprint was already available for the community just before the pandemic.(19:17):As it happens, we also took a step forward with our policy. So previously, let's just say we were completely fine with preprints. We saw preprints as compatible with submission to, to Nature, and for that matter to the other journals in the Nature Portfolio. But actually just in the year before COVID started, we decided to actively encourage our authors to deposit preprints. We could see that preprint sharing had great advantage. You know, the, the usuals of advantages, which are often listed first are of course ability to make that primacy claim, make a stake that, that you have been working on something and, and this is your project. You have a set of results that you are ready to communicate to, to the community at large. And of course, another very important one is that sort of community and, and almost public form of peer review and, and ability to comment.(20:30):And incidentally, I remember as you know, my, my history as an editor very well. We've known each other for a long time. I remember when the genomics community, which is sort of my, my background is sort of my old hat, if you like, that, that I used to wear when the genomics community began to embrace preprints especially the population and evolutionary genomicists really embraced this idea that this was like a group peer review. And the authors of those preprints were very grateful to the community for improving the papers before they were submitted to journals, or sometimes that sort of community review was going on while a paper was being considered at a journal. And we, as editors actually encouraged sort of formal submission of these reviews, if you like, I mean, formal maybe is the wrong word, but we were saying that we would take those comments into account when evaluating papers.(21:38):So there has been an interesting evolution that more and more disciplines, more and more fields have embraced preprints as a way of disseminating information. Preprints service themselves have also grown and matured in the sense that there is now realization that, for example, clinical preprints need a higher degree of scrutiny they're posted on a preprint server than maybe let's say theoretical physics or theoretical biology preprints. So overall all communities collectively have grown and matured. Where are we going with this? I mean, who knows? I was predicting 12 years ago you know, a bit of a different, more advanced future today. It's very difficult to predict the future. I do think, however, that what we are seeing today, that sort of hand in glove coexistence of preprints with journals, with peer reviewed papers is going to continue into the future. And I think actually that's a really valuable and interesting combination. So it's a great development to see and great to see that communities right across disciplines have really embraced this.Eric Topol (23:11):Yeah, I think it does complement, obviously the traditional peer review of a few expert reviewers with, you know, could be hundreds if not thousands of people that weigh in on, on a pre-print. So yeah, it's fascinating to see. And it's, I still remember the vision that you portrayed for it, and how we we're not quite there yet, but I'm sure there'll be further evolution.Women in Science: Where Do We Stand?Now, another area that I think is particularly good to get your input, because you're a woman in science, as you mentioned, you know, grounded obviously in genetics and genomics, and here you are, one of the most influential women in science at a time when there's been a reckoning that women in science have been shortchanged historically, I mean, for hundreds of years. Do you see that this is starting to get better? Are there palpable signs that we're finally getting kind of equal rights here? Or are we, is it, is it just still a long fight ahead?Magdalena Skipper (24:20):So the, the optimist in me and, and I should say, you know, my, my glass, my glass is always half full. The optimist in me says that it is getting better, but the realist in me has to add immediately that the changes too slow. It really is too slow. We do see many more women prominently able to make the contributions that they should, they can, and they should make to whatever discipline whatever aspect of the research community and beyond they wish to, to make. I still think it costs them too much. I still think we don't appreciate and support women sufficiently.(25:23):Maybe we have moved on the bottleneck in the, in the pipeline a little bit further, towards more seniority. But we still, we still don't sufficiently support women. As I say, we, I think we still default to an expectation that successful women in science in research more broadly will somehow emulate how success has looked in the past. And that's a shame, that's a shame not just for those women who are trying to come in and make a difference, but it's a shame for all of us because it means that we are denying diversity in that picture of success. Yes. So yes, I think, I think that we have seen many changes, but I think the change is not happening fast enough.Eric Topol (26:23):Yeah. One of the things that I've noticed since of particular interest in AI is that the very profound imbalance of researchers, the gender imbalance there is just, you know, I'm not even sure if it's 10% women researchers in AI, so that has to be changed. And so this, there's so many things that are holding us back, but, but that's certainly one of, of many.Magdalena Skipper (26:49):Absolutely. And, and, and if I can just add, there are some outstandingly influential female researchers in the AI field, as you say, they are just outnumbered. Yes. , I think not given the opportunity to, to fully blossom, if you like, considering their capabilities and, and their contributions already.Eric Topol (27:11):You know, it's so true. I just interviewed Melanie Mitchell from the Santa Fe Institute, and I work with Fei- Fei Li. And when I, when Fei-Fei Li and I spoke some months ago about a book (Genius Makers) that Cade Metz, the New York Times journalist had written, and I say, why didn't he bring up or emphasize the role of any women in the whole book . Yes--who work in A--I mean, she, she obviously was, was did not take that particularly well, and as did I.Too Many Nature Portfolio Journals?So one of the other areas that I think you already touched on, which is separating Nature, the flagship journal from the Nature Portfolio of, I don't know what it's up to now, 200, 300, I'm not sure how many journals are. So do you, do you have to over oversee that? Do you have input on that? Because what I worry about is, you know, people quote a Nature journal and it may not be, you know, at that level that you would be proud of. What, what are your thoughts about this endless proliferation of the nature portfolio?Magdalena Skipper (28:17):Well, I, I'm, first of all, I'm not sure if it's endless, butEric Topol (28:20):Oh, that's good. .Magdalena Skipper (28:22):So, so let me, I think in your question, you touched on a number of things. So first of all, a clarification. So my role is as Editor-in-Chief of Nature, and of course, that is my main focus. there is another aspect to my role, which is Chief Editorial Advisor for the Nature Portfolio. So in that sense each of the journals within the Nature portfolio has its own chief editor. but by virtue, I guess, of my seniority, and also by virtue of multi-disciplinarity of Nature I have this advisory role to my colleagues in the other journals. I like to think about the Nature Portfolio as an ecosystem, actually. And it's an ecosystem, like any ecosystem. It has different niches, each of which fulfills a different role. Some of them are bigger, some of them are smaller, some of them are very specialized, others are more general.(29:22):And I think you know, working with researchers for many years as an editor now, I can see benefits to having that sort of almost an ecosystem type approach to publishing. You know, for example, we mentioned already earlier that in my previous sort of incarnation as an editor, my focus was on genomics especially in the context of human genomics. of course starting from the Human Genome Project, these were very large or have, where, why, why am I using past tense? They are, to this day, very large collaborative projects involving many different labs, many different approaches these days that they're not just focused on genomics, but of course other omics go hand in hand with them. So when a project comes to fruition, when, when it comes to be published, there are many different pieces that need to be communicated, many different papers of different sizes of different value.(30:32):And for example what value maybe is the wrong word of different utility? So, for example, there may be a flagship paper that is published in the pages of my journal of Nature, but there may be papers that specifically described development of methodology that was part of the same stage of the project. And those papers may be published in Nature Methods, which is part of the Nature Portfolio. There are other journals that are part of Nature Portfolio, which have different editorial bar. And so, you know, one example is Scientific Reports, which is a journal which does not require conceptual novelty in the papers that it publishes. Of course, it requires rigor and, and robustness in the papers that it publishes, like every journal should. But there is utility in publishing papers in a journal like this.(31:36):There may be replications that are published there that further add further evidence to support conclusions that are already well known, but nevertheless, they're useful. I should however, add that in Nature itself, we also publish replications, right? There are different degrees of influence and impact that, of course, different studies be there, replications or not that can carry. So, that will be my way of conceptualizing the Nature Portfolio. and, you know, coming back to your, to your comment that it seems like it's endless. I think well, nothing, nothing is endless. Of course. Nothing, nothing, right, grows forever. I do think that we have in the launches within the portfolio, we have been able to capture and at the same time serve an interesting evolution in the research ecosystem itself. So the final comment I will make on this is, if you look at some of the more recent launches in the portfolio, they've been what we like to call thematic journals, such as, for example, Nature Food or Nature Water.Eric Topol (33:10):Right?Magdalena Skipper (33:10):And here we are really capitalizing on that multi-disciplinarity of these emerging themes that, especially in the context of sustainable development goals, have acquired their own identity. They don't belong to one discipline or another discipline. And, and so these journals, they're new journals, relatively new journals, some of them very new Nature Waters is, is quite new, but they provide a focal point for researchers who come together to solve a particular set of problems from different disciplines. And I think that's an interesting function in, as I say, for the community.What About the Paywalls?Eric Topol (33:53):Yeah, there's no question some of the newer journals and their transdisciplinary mission --they're needed and they become extremely popular and well -cited very quickly to prove that. So along that line obviously the public is all fired up about paywalls and you know, and obviously for Covid, there was no paywalls, which is pretty extraordinary. Do you see someday that journals will have a hard time of maintaining this? I mean, you have what I consider an extraordinary solution, which is the ReadCube postings anyone can access, you just can't download the PDF, and I wish authors would always routinely put that out there because that would solve part of the problem. But do you think we're going to go to a free access that's much more wide, perhaps even routine, in the years ahead?Magdalena Skipper (34:52):So certainly open access as in ability to access a manuscript, published manuscript without any payment or barrier associated with a Creative Commons license is something that is advanced as a, as a preferred future by many researchers, by many funders. and for that matter, actually many publishers as well. You know, let me make one thing very clear. As an editor, I would love as many people as possible to read the papers that I publish in my journal.Magdalena Skipper (35:30):That should go without saying. Sure. at the same time, publishing papers, of course, is associated with a cost, and, and that cost has to be somehow covered. In the old days it was exclusively covered by library subscriptions or site licenses or personal subscriptions. Now the focus is shifting. And of course, Nature itself as well as the other research journals such as, for example, Nature Medicine or indeed Nature Water, as I mentioned before are what we call transformative journals. So effectively we are hybrid journals that advocate for open access. So today, when you submit a paper to Nature, you can publish under the traditional publishing model, or you can choose to publish open access, which is associated with an article processing charge. That should, in my view, be part of your costs of doing research, because after all, I'm a firm believer in the fact that publishing your research should be seen as part of doing research, not sort of an add-on.(36:47):Now, I'm glad you mentioned read Read Cube and this functionality that we call shared it. We developed it actually quite some years ago. I would say at least a decade ago. it remains curiously underappreciated. Yeah. I just don't understand it. Yeah, exactly. And, and we, we inform the authors that they are free to use that link. And, and just to clarify, it's a linked as you exactly as you explained to an online version of the paper. It's the final version, the record version of the paper. You can't download it, but you can share that link. Anyone can share that link once they have it Infinite number of times. So it's not like the link expires, or it's a, a finite number of, of that it has a number of finite number of uses in addition to that nature.(37:49):And for that matter, the whole of Springer Nature is part of Research4Life. Now, that's an organization that provides free access to all content from publishers. And Springer Nature is not the only publisher that's part of Research for Life that provides full access to all of our content in the countries which are designated as low and middle income countries by the World Bank. So that we've been part of that. And, and previously for many, many years, in fact, decades, again, that is curiously underappreciated, including in the low and middle income countries. So, you know, recently had an opportunity to do some visits in Africa. And my, my take home message there was, if there is one thing that you remember from our conversation or from my presentation, please remember about Research4Life.Magdalena Skipper (38:52):Because that content is freely available if you follow, if you go to our content through Research4Life. And incidentally, there's also training, which is available there. So part of Nature portfolio in addition to journals, we have Nature Master classes, which is training for researchers. And that is also completely freely available in those countries. So there are a number of approaches to, to getting content open access is definitely growing, but there are those other ways to gain access to content which is not open access at the moment.Eric Topol (39:33):I'm really glad you reviewed that because a lot of people who are going to be listening are going to really cue into that. Now the last question for you is, you know, it's not just every Wednesday, 51 or whatever, 50 weeks a year, that you're getting the journal ready, but it's every day now that you're putting out stuff and on the Nature website. Features that are by the way, free or full access and many other things to keep Nature out there on a daily, if not minute to minute basis. So this is really a big charge to, you know, do this all so well. So what keeps you up at night about Nature is this, this must be a very tough position.Magdalena Skipper (40:28):So the first thing I would say that is that of course it's, it's not me. I'm just the person here talking to you representing Nature. I have an outstanding team.Eric Topol (40:44):I've met them, and they're amazing.Magdalena Skipper (40:46):And it's really them who are making it possible on a minute by minute, certainly day by day basis. And so the reason why I sleep relatively well is thanks to them actually, okay,Eric Topol (41:00):. Okay.What Keeps You Up At Night?Magdalena Skipper (41:01):But more, but more broadly. and this is a thought which is bigger than Nature itself. What actually keeps me up at night these days is the rather difficult light in which science and research is portrayed these days increasingly.Magdalena Skipper (41:27):And I think it's very unfortunately being to support other goals and other ends forgetting about the fact that science is an ongoing process that science takes steps back when it needs to revise its position, that it still continues to be true, that s science progresses through self-correction. Even if that self-correction doesn't happen overnight, it takes time to realize that a correction is required, takes time to evaluate judiciously that correction is required and what kind of correction is required, right? These are the things that of course, you and I know very well. But the, sometimes if for individuals who are not close to the process of how science research fact-based discovery is conducted, if you just look at information on social media or in general media, you may walk away with an impression that science is not worth paying attention to that science is in some deep crisis.Magdalena Skipper (43:04):And I think that's, that's a shame that that's a picture that we have other things that need other things in science, in research that need correcting, that need sorting out. Of course, we mustn't forget that research is done by humans and, and after all it is human to air. But overall, that's actually something that keeps me up at night. That overall, I really hope that those of us who are engaged in one way or another within the research enterprise, we can continue to advance the right kind of image that it's not perfect in some artificial way, but actually, at the same time, it's the only way that we can move forward. We can understand the world around us, and we can wake, make the world around us better, actually.Eric Topol (44:11):Yeah. I'm so glad you've emphasized this because just like we talked earlier about distinguishing between human and AI content generated here, we have science and anti-science blurring facts, blurring truths, and basically taking down science as a search for truth and making it trying to, you know, obscure its mission and, in many ways, we, we saw it with not just anti-vax, but it's much bigger. The political motives are obvious extraordinary, particularly as we see here in the U.S. but other countries as well. So I almost didn't hit you for that question, just because it's so profound. We don't have the answers, but the fact that you're thinking about it tells, tells us all a lot. So Magdalena, this has been a joy. I really appreciate all your candid and very thoughtful responses to some of these questions.(45:09):Some of them pretty tough questions I have to say. And I look forward to our conversations and chances to visit with you again in the future. And congratulations again on taking on the leadership of Nature for five years now-- I believe just past your five-year anniversary now. You could say that's small out of 155 years, but I think it's a lot. particularly since the last few years have been, you really challenging. But to you and your team ultimately –-major kudos. I'm on the Nature website every single day. I mean, even, I when I'm on vacation, I'll be checking out the Nature site. So you can tell that I think so highly of the its content and we'll look forward to future conversations going forward.Magdalena Skipper (45:52):Thank you very much. Thank you very much, Eric. It's always a pleasure to talk to you. Thank you. Get full access to Ground Truths at erictopol.substack.com/subscribe
When scientists want to know about genes, chances are they use instruments called sequencers. There are quite a few companies that make sequencers. These instruments can give a read-out for example of a stretch of DNA or many stretches of DNA, even entire genomes and many genomes. The challenge has been that the instruments deliver--short reads—short readouts of sequence. What happens then is that scientists face the challenging computational task of stitching together short reads into contiguous sequence. But long-read sequencing is a way to address this challenge. The method of the year according to Nature Methods is: long read-sequencing. For a story I chatted with scientists at companies and in academia about long-read sequencing. This episode is with Dr. Jonas Korlach, chief scientific officer of Pacific Biosciences, which is one of the companies that offers instruments that can do long-read sequencing. (Art: J. Jackson. The following music was used for this media project:Music: Winnie the Moog, Funky Energetic Intro and Acid Trumpet by Kevin MacLeod Free download: https://filmmusic.io/song/3340-acid-trumpet License (CC BY 4.0): https://filmmusic.io/standard-license0
When scientists want to know about genes, chances are they use instruments called sequencers. Some of them can generate long-reads, which helps with analyzing genomes. The method of the year according to Nature Methods is: long read-sequencing. For a story I chatted with scientists at companies and in academia about long-read sequencing and did some podcasts, too. This episode is with Dr. Gordon Sanghera, CEO of Oxford Nanopore Technologies. (Art: J. Jackson).The following music was used for this media project: Winnie The Moog, Funky Energetic Intro and Acid Trumpet by Kevin MacLeod Free download: https://filmmusic.io/song/3340-acid-trumpet License (CC BY 4.0): https://filmmusic.io/standard-license
ヒトの細胞で人工的なクオラムセンシングの構築を目指した論文を紹介しました。Shownotes Synthetic mammalian signaling circuits for robust cell population control. Cell 2022 … 今回sohが紹介する論文です The Elowitz Lab at Caltech Quorum sensing (Wikipedia) 80. Guest explains everything (Researchat.fm) … Pomeさんをゲストに迎え、CAR-T治療などについて教えていただいた回 Nishimura et al. Nature Methods 2009 … “An auxin-based degron system for the rapid depletion of proteins in nonplant cells” Blasticidin S DamID Editorial Notes 随分と収録から公開の間が空いてしまいましたが引き続き論文を紹介していきます (soh) Quorum sensingおもしろいなぁ(tadasu)
Models are important tools: they resemble, they mimic, they imitate something to a greater or lesser extent. How similar models are to the 'real thing' is usually a challenging issue. And it's a big issue with stem-cell derived models of the human embryo.These embryo models, models of the embryo's 8-cell stage, of the blastocyst or of the gastrula are emerging and they are ones that labs can use to characterize the molecular and physiologic events that take place during early embryogenesis. My story in Nature Methods about some of these embryo models is here. For this story, I spoke with Christine Mummery, a researcher in the anatomy and embryology department at Leiden University Medical Center. In this podcast, she talks about models of the blastocyst and the gastrula, about the updated International Society for Stem Cell Research (ISSCR) guidelines, and shares some thoughts about about what is involved when assessing a model. "If I'm claiming this is a liver cell, what does it have to show? And this is a tricky, tricky thing," says Christine Mummery.
I asked Dr. Leo Poon, who co-directs the Hong Kong University Pasteur Research Pole, if he has a fleet of private jets. He does not. But he wishes he did. He and his team have helped colleagues all over the world on COVID-19. He and his team developed a diagnostic assay quite soon after the genome sequence of SARS-CoV-2, the virus that causes COVID-19 became known. His is the lab that detected and identified SARS, the outbreak in 2003. And many other viruses. Like most science journalists, I report on COVID-19 and I had been wondering about researchers in the Global South and their COVID-19 related research. Here is the story I did for Nature Methods https://www.nature.com/articles/s41592-022-01439-w. For that story, I spoke with Leo Poon about his work during the height of COVID-19 and now and his outlook for the future. This podcast is more from that conversation. (Art: J. Jackson)
Utiliser le deep learnin (lʹapprentissage profond) pour étudier les mouvements des animaux, cʹest ce que font des scientifiques de lʹécole polytechnique fédérale de Lausanne (EPFL) à lʹaide dʹun logiciel nommé DeepLabCut. Grâce à cela, ils parviennent à analyser les comportements dʹanimaux seuls, mais surtout en groupe. Leurs résultats sont à lire dans la revue Nature Methods. Plus dʹinformations avec Jessy Lauer, docteur en biomécanique, spécialiste du traitement des images à lʹEPFL, un des concepteurs de DeepLabCut-Live et premier auteur de l'étude en question. Un sujet préparé par Sarah Dirren.
Virologist Dr Marycelin Baba from the University of Maiduguri in northeastern Nigeria is passionate about her work on viruses, She runs a World Health Organization (WHO)-accredited and WHO-sponsored lab where the team has worked, for example, on polio. When COVID-19 emerged, she and her team were prepared and she was called upon to help build capacity in Nigeria to address COVID-19. When the government asked her to certify a lab not up to biosafety levels, she said no. "Even if I was to be killed, I don't mind," she says. This is episode 1 of a series of podcasts about the grit and determination scientists in the Global South are putting to work against COVID-19. It's not, in my view, a downer of a story. It goes along with a feature I did for Nature Methods called 'Lessons from the Global South's fight against COVID-19.' That story is here: https://www.nature.com/articles/s41592-022-01439-w
Proteins are twirly, curly, dynamic structures. Crucial for life, complicated to study. Predicting protein structure has been tough but it's now easier as AlphaFold enters the scene. That doesn't mean that AlphaFold has solved all challenges, of course. AlphaFold was developed by DeepMind Technologies, a company that was bought by Google in 2014. Lots of protein puzzles remain. Dr. Janet Thornton from the European Bioinformatics Institute and Dr David Jones of University College London talk about what AlphaFold can do and what it cannot yet do. They look forward, backward and all around on this subject. He says, laughing, he has "extreme cautious optimism" about the prospects of this field. You can also find my feature story about protein structure prediction, which is the Nature Methods method of the year for 2021, here: https://www.nature.com/articles/s41592-021-01359-1
In this episode we interview Cath Lee, Lar Lee and Matt Crane - founders of Semaine Health, "a health and wellness company that takes women's pain seriously". Cath and Lar, twin sisters, describe their personal journey with endometriosis and years of period pain. Together with Matt (Lar's husband), they started experimenting with trying natural plant-based ingredients, vitamins and supplements, to help alleviate pain, decrease inflammation, improve digestion and mood, while also doing research on existing evidence. This research and experimentation ultimately lead them to creating a plant-based supplement and starting a company called Semaine Health. The supplement has 9 clearly listed ingredients and Matt describes how they play a role in supporting a healthy body during period time - for example magnesium, Vitamin D, or curcumin. Lar and Cath share their passion for building a community, where talking about women's health, including period pain and menopause is normal. Tune in to learn more about their story!Catherine Lee was born and raised in Maryland in the suburbs of D.C. She graduated from Agnes Scott College and got her MPA at Georgia State. For 15 years she did economic development for the cities of Decatur and Chamblee, Georgia. In 2019, Catherine, her twin sister and brother-in-law, created Semaine Health, a womxn's wellness company that creates all-natural, science-backed solutions to common problems like period pain, hormone imbalances and UTIs. Semaine products are currently sold online, Thrive Market and at Target stores nationwide. Catherine lives in Decatur, GA with her rescue dog, is an ENFJ and loves to talk all things about womxn's health.Lauren Lee calls Atlanta home, but originally hails from the metro DC area. She graduated magna cum laude from Agnes Scott College and launched her 15 year career in graphic design, art design and creative leadership. Lauren worked for award winning agencies both in the US and UK, and pursuing her travel dreams around the world. In 2019 she cofounded Semaine Health Co., a plant-based supplement company that supports and finds solutions for women at every stage of her life, from her first period through menopause (and every UTI in between). Lauren uses her creative background to help women feel empowered about their health and health choices, and is passionate about making the wellness space more equitable and inclusive.Matthew Crane completed his BS and MS at Case Western Reserve University. He completed his PhD in Bioengineering at Georgia Tech, where his work was highlighted by The New York Times, The Scientist and Nature Methods. Matthew completed postdoctoral research at the University of Edinburgh and the University of Washington. He joined the University of Washington School of Medicine faculty before leaving in 2019 to help start Semaine Health. He is passionate about designing natural products that take a rigorous and clinical approach to help address common but neglected problems. Check out Semain Health website to learn more!This podcast is brought to you by Emory Lifestyle Medicine & Wellness. To learn more about our work, please visithttps://bit.ly/EmoryLM
One of the biggest challenges when it comes to probing and manipulating the brain are the blunt tools we have at our disposal. But breakthroughs in nanotechnology could soon change that, say researchers. Neuroscience has experienced a technological revolution in the last couple decades thanks to rapid improvements in brain-machine interfaces and groundbreaking new methods like functional magnetic resonance imaging, which makes it possible to track neural activity across the whole brain, or optogenetics, which makes it possible to control individual neurons with light. But despite this progress, we are still a long way from being able to record or stimulate large parts of the brain at the single-neuron level. Being able to do so could have profound implications on our understanding of the brain, as well as our ability to augment its function and treat disease. The key to bridging this gap is the emerging field of “NanoNeuro,” say the authors of a new paper in Nature Methods. The unique properties and diminutive size of nanomaterials could make it possible to probe neural circuits in entirely new ways and at previously unimaginable scales, the researchers write. The most obvious application of nanotechnology is in simply reducing the size of the standard neuroscience toolbox. A host of recent designs for nanoprobes and nanoelectrodes, often exploiting the same processes that have powered the miniaturization of computer chips, are making it possible to record from orders of magnitude more neurons. These probes often come with other desirable properties too, such as flexibility, optical functionality, or chemical sensing. Other materials such as quartz, carbon nanotubes, and graphene are also being experimented with and each have their own unique properties. Perhaps most importantly, these tiny electrodes open the door to probing neural activity at the sub-cellular level. Given the powerful processing that goes on within neurons, this could significantly improve our understanding of critical aspects of brain function. Nanotechnology isn't just about making things smaller, though. Physics operates on very different principles when you get down to the scale of atoms and molecules, which means nanomaterials can have exotic properties that enable entirely new functionality. For example, plasmonic nanoparticles have unique optical properties that can be easily tuned by simply varying their size and shape. These particles could be used to boost the sensitivity of existing optogenetic approaches, say the authors, and using light to excite and heat them up could also make it possible to trigger neurons to fire with very high precision. Even smaller “quantum dots”—nanoparticles that emit light in various colors when energy is applied to them—are a more durable and sensitive alternative to fluorescent dyes currently used for imaging. Their fluorescence is also modulated by electric fields, so they could potentially be used to give an optical readout on the activity of neurons. Another promising class of nanoparticles can absorb multiple low-energy electrons and convert them into a high-energy one. Researchers have used these so-called “upconverting nanoparticles” to let mice see in infrared by injecting them into the animals' retinas, where they translate incoming signals into visible light. Potentially the most powerful application, though, could come from magnetic nanoparticles. The human body is almost entirely unaffected by magnetic fields, which makes it possible to send them deep into biological tissue with little impact. Nanoparticles that can convert magnetic fields into stimuli that trigger neurons could be a powerful tool to modulate brain activity. There's still a long way to go, according to the authors. Effectively delivering nanoparticles to where we want them is challenging, as is producing large numbers of them without too much variability. And while early studies suggest many nanomaterials are biocompatible, proving they...
The brain is the center of every human being's world, but many of its inner workings are yet mysterious. Slowly, scientists are pulling back the veil. Recently, for example, researchers have created increasingly intricate maps of the brain's connections. These maps, called connectomes, detail every cell and synapse in small areas of the brain—but the maps are static. That is, we can't watch the cellular circuits they trace in action as an animal encounters the world and information courses through its neural connections. Most of the methods scientists use to watch the brain in action offer either low resolution and wide coverage or high resolution and narrow coverage. A new technique, developed by researchers at The Rockefeller University and recently published in the journal Nature Methods, is the best of both worlds. Called light beads microscopy, the team was able to record hundreds of thousand of neurons in 3D volumes through time. In a striking example, they released a movie of a million neurons firing in a mouse brain as it went about its day. Typically, neuroscientists use a technique called two-photon microscopy to record neurons as they fire. Laser pulses are sent into the brain where they interact with fluorescent tags and cause them to light up. Scientist then interpret the light to infer activity. Two-photon microscopy can record small bands of neurons in action, but struggles for bigger groups. The light beads technique builds on two-photon microscopy, with a clever tweak. Instead of relying on single pulses too slow to record broad populations of neurons firing, it divides each pulse into 30 sub-pulses of varying strengths. A series of mirrors sends these sub-pulses into the brain at 30 different depths, recording the behavior of neurons at each depth almost simultaneously. The technique is so speedy that its only limitation is how quickly the fluorescent tags respond to the pulses of light. To test it, the team outfitted a microscopy platform—essentially a lightweight microscope that can be attached to a mouse's head to record brain activity as it moves about—with the new light beads functionality and put it to work. They were able to capture hundreds of thousands of neurons signaling to each other from across the cortex. Even better? Because light beads builds on already-widely-used two-photon microscopy, labs should already have or be able to readily procure the needed equipment. “Understanding the nature of the brain's densely interconnected network requires developing novel imaging techniques that can capture the activity of neurons across vastly separated brain regions at high speed and single-cell resolution,” Rockefeller's Alipasha Vaziri said in a statement. “Light beads microscopy will allow us to investigate biological questions in a way that had not been possible before.” But the technique won't replace standard two-photon microscopy, Vaziri says. Rather, he sees it as a complementary approach. Indeed, the growing quiver of imaging technologies, from those yielding static wiring diagrams to those recording function in vivo, will likely combine, quilt-like, to provide a far richer picture of how our brains do what they do. Researchers hope this kind of work can shed light on how the brain's complex networks of neurons produce sensations, thoughts, and movement, what causes them to malfunction, and even to help us engineer our own intelligent systems in silicon. Image Credit: Alipasha Vaziri / The Rockefeller University
This podcast is with Dr. Hongkui Zeng who directs the Allen Institute for Brain Science and Dr. Bolisjka Tasic who directs Molecular Genetics at the Allen Institute for Brain Science. It's about how spatially resolved transcriptomics, a Nature Methods Method of the Year, can help to understand the brain. I did a story about it here: https://www.nature.com/articles/s41592-020-01033-y . This is a podcast series that shares more of what I found out in my reporting. The piece is about smoothies, fruit salads, fruit tarts, genomics and a big puzzle called: the brain. Transcript of podcast Note: These podcasts are produced to be heard. If you can, please tune in. Transcripts are generated using speech recognition software and there's a human editor. But a transcript may contain errors. Please check the corresponding audio before quoting.Not lost in space Episode 2 Hi and welcome to Conversations with scientists, I'm Vivien Marx. This podcast is about space--space in biology, actually. Talking about the role of space and spatial analysis in biology is a chat about food. About smoothies, fruit salads and fruit tarts. Here's Dr. Hongkui Zeng and Dr. Bosiljka Tasic from the Allen Institute for Brain Science. [0:30] Bosiljka Tasic Fruit salad and smoothie. Fruit tart is spatial transcriptomics.Smoothie is Bulk RNA-seq. Ok passé Hongkui ZengForget it. Bosiljka Tasic You have fruit salad, you have dissociated cells you are profiling, you have lost the context, you have a context in the piece of tissue you have dissected. Then there is the fruit tart. You know exactly where each piece of fruit. Relationship to the other VivienOk so spatial analysis in genomics is understanding a fruit tart. Knowing which genes are expressed where and what the relationship is of the genes to one another. The two scientists will talk more about this shortly. There's Dr. Bosiljka Tasic, she directs Molecular Genetics and her research is for example on cell types in the mouse brain. And Dr. Hongkui Zeng who is director of the Allen Institute for Brain Science. Before they explain more about this science, here they both are, kindly teaching me how to pronounce their names. As ever I will try to do this right. And likely fail. [1:37] Bosiljka Tasic and Hongkui ZengI'm Bosiljka Tasic. Bosiljka Tasic. OK, got it Hongkui Zeng. You don't pronounce the G at all, just, well, Zen, yeah, Zen G Zen. Yeah, yeah. It's very, very almost not there. How would you how would you pronounce that if you emphasize the G . ZengG. So I think g you hear much more but it's not the correct way. I mean I've given you my Americanized way of saying my name. I see. Well I'm going to, I'm going to do it wrong anyway. But but at least for me, don't worry. VivienNext, before we get back to their thoughts and research, just a bit about this podcast series. In my reporting I speak with scientists around the world and this podcast is a way to share more of what I find out. This podcast takes you into the science and it's about the people doing the science. You can find some of my work for example in Nature journals that are part of the Nature Portfolio. That's where you find studies by working scientists and those are about the latest aspects of their research. And a number of these journals offer science journalism. These are pieces by science journalists like me. This podcast episode about space in biology harkens back to interviews I did months ago. Back then I asked scientists about their work and their thoughts about spatially resolved transcriptomics, which is a Nature Methods method of the year. In my slow pokey DIY podcast production this is episode 2 in a series about this field of study. Spatially resolved transcriptomics helps with studying the brain, which is the giant puzzle that Hongkui Zeng and Bosiljka Tasic work on. Among their daily puzzles is: How many different cell types are there in the brains of mammals such as mice, primates or humans? There are lots of them. And scientists want to be more precise than just saying there are lots of cells, of course. They want to know which ones there are and where they are. In the brain, another puzzle is where are cell types when. Cells are born and then often move to other areas of the brain where they will tend to all sorts of tasks. It takes a number of techniques to address these questions, including spatial techniques. The US National Institutes of Health—NIH--has many research projects, one of them is the Brain Initiative, NIH's Brain Research through Advancing Innovative Neurotechnologies Initiative. Part of that is the NIH Brain Initiative Cell Census Network (BICCN). One big BICCN project is to build a high quality atlas of cell types in the entire mouse brain. Many labs are working together to produce human, mouse and non-human primate brain atlases, these are intended as references for labs around the world. The scientists use imaging, electrophysiology and molecular genetic analyses including analysis of gene expression, which is transcriptomics. BICCN phase 1 is underway and phase 2 is getting underway. The project has started with the mouse brain and is moving toward an atlas of the non-human primate brain and the human brain. One big challenge in this venture is distinguishing cell types. Cells may look very different but they might also look quite similar to one another. Here is Hongkui Zeng talking about BICCN [5:20] Hongkui ZengWe are currently in phase one, BICCN phase one, building this brain-wide cell type reference atlas. We are doing quite well and we expect to complete phase 1 in the next two years. And then phase 2 is starting, BICCN, phase 2 what you heard at SfN. There are several major themes for phase 2 that were announced by NIH. The three major themes are building cell-type targeting tools, moving into the study of primate brains including human brain, cataloging cell types in the human brain and then finally studying the connections, the connectomics of the human brain. Bosiljka is very active in one of those initiatives, which is building in one of cell type targeting tools Bosiljka Tasic You want to define a cell type first, but then you want to be able to access it for experimental examination perturbation. You want to form causality connections between a cell type and, let's say a specific behavior. So in order to do that, you need to build usually a genetic tool that is based on genes that are expressed in the cell type or maybe regulatory elements, enhancers that are active in that cell type. You can you can create a transgenic mouse or a viral tool that will then deliver a particular transgene, a particular perturbing or labeling gene to that cell, and then you can visualize the cell, monitor it, maybe monitor its activity or perturb it and ask for Phenotypes effects at the level of that cell, at the level of the circuit, at the level of the whole organism. And both Hongkui and I, we are we have a just...
This podcast is about two scientists, Dr. Patrik Ståhl and Dr. Fredrik Salmén, who are joint first authors of a paper that kickstarted a field. It's about finding work they did with colleagues to enable finding out where in tissue gene expressions is happening. It's called spatially resolved transcriptomics. It is a Nature Methods Method of the Year and I did a story about it here: https://www.nature.com/articles/s41592-020-01033-y . This is a podcast series that shares more of what I found out in my reporting. The piece is about patience, stamina, friendship, surfing the Baltic Sea, genomics and imaging. [00:00:05.560] - Vivien MarxHi and welcome to Conversations with Scientists, I'm Vivien Marx. This podcast is with and about two scientists and about space space in biology. Actually, you'll meet Patrik Ståhl. He's on the faculty of KTH Royal Institute of Technology in Stockholm, Sweden, and Fredrik Salmén, who is currently a postdoctoral fellow at Hubrecht Institute in the Netherlands. They will talk about a field.[00:00:33.280] - Patrik StåhlThe whole field. It's really it's it's an awesome field.[00:00:36.940] - Vivien That's Patrik Ståhl. Their work led to a major publication in the journal Science, and they are both joint first authors of this paper,[00:00:47.710] - Patrik StåhlWe share the honor[00:00:47.710] - Fredrik Salménand the pain.[00:00:47.710] - Vivien The honor and the pain. That's research for you. Just briefly, before we get to that about this podcast series, in my reporting, I speak with scientists around the world, and this podcast is a way to share more of what I find out. This podcast takes you into the science, and it's about the people doing the science. You can find some of my work, for example, in Nature journals that are part of the nature portfolio. That's where you find studies by working scientists.[00:01:19.960] - Vivien And those are about the latest aspect of their research in a number of these journals offer science journalism. These are pieces by science journalists like me. This podcast episode is one of several I'm producing about space in biology. Months ago, I interviewed researchers who work on Spatially resolved transcriptomics for a story and in my slowpokey DIY podcast production. This is part one in a series about this field of study. So Patrik Stahl and Fredrik Salmen here they are introducing themselves to help me learn how to pronounce their names.[00:02:02.890] - Patrik Ståhl Fredrik you go first.[00:02:03.560] - Fredrik SalménFredrik Salmén. [00:02:12.290] - Vivien All right. I have to practice. OK, so in[00:02:16.750] - Patrik StåhlEnglish it's Patrick. It's Patrik Stahl.[00:02:21.650] - Vivien Patrick Sahl? So no t, Stahl[00:02:29.210] all right, you have to brace yourselves.[00:02:33.980] - Patrik StåhlStahl means steel in English,[00:02:36.393] - Patrik StåhlPatrik Ståhl[00:02:36.780] - Vivien Wow I apologize . Despite their lessons, I am doing the Swedish pronunciation of their names badly. I hope they and Sweden will forgive me. So I interviewed these two Swedish scientists together and when we started to chat, I noticed a poster on the wall behind Fredrik Salmen. It showed a surfer riding a big wave. So I asked about that.[00:03:03.530] - Patrik StåhlFredrik actually quite advanced surfer, like wave surfer at the time when we started this project.[00:03:14.540] - Fredrik SalménYah, it's true. Oh, it's actually me. It's a little bit self-centered, I guess, to have their own picture on the wall. But it's fun, though. It's[00:03:27.620] - Vivien where was this taken?[00:03:30.290] - Fredrik SalménThis is actually Sweden. So it's the Baltic Sea.[00:03:35.900] - VivienThe Baltic Sea is cold. You need to wear a special suit if you want to surf there.[00:03:41.240] - Fredrik SalménYeah. It's like a frog suit with hood and gloves and boots.[00:03:45.920] - VivienSo do you still do this or.[00:03:48.320] - Fredrik SalménYeah, I still do. I'm a little bit, I would say much less nowadays and I'm also a little bit heavier these days, so not as agile anymore. But still when I get the opportunity I try to surf, it's nice. [00:04:06.020] - Vivien The two researchers worked together along with many others, but their connection was quite intense and you will hear more about that in this podcast.[00:04:13.260] - VivienIt was work that took around six years and led to a publication in the journal Science. And that publication kick-started a field. And there was a company spin out to the field of study is called spatially resolved transcriptomics, and it was crowned a Nature Methods method of the year. In this area of spatially resolved transcriptomics, scientists want to know where something takes place. It's part of understanding larger issues, such as why does the head grow where it does?[00:04:44.750] - Vivien Why does a part of the brain develop where it does? Why does a tumor grow where it does? It's genes that tune such events, genes are turned on or off, they are expressed at high levels or low levels or silenced, their expression can shift. With gene expression, it's like tissues are playing a kind of music, just one you need to find ways to hear. Patrik Stahl and Fredrik Salmen and their colleagues found one way to do just that.[00:05:15.370] - Vivien The work took place in Sweden. It involved surfing the cold waves of the Baltic, as you just heard. It's about friendship. It's about patience, about science, careers. If you're interested in any of that, as well as biology, genomics and imaging, please stick around. So this work in particular took six years and Fredrik Salmen and Patrik Stahl worked intensely together. They are the first authors of this paper in Science published in 2016, and it led to a company called Spatial Transcriptomics.[00:05:45.790] - Vivien What these scientists and their colleagues developed was a way to see where, for example, in a tissue genes are expressed. It's not the first way to do this, but it was a way to analyze a lot of mRNAs, a lot of gene transcripts at the same time. To understand why this matters, we can step back for a moment and consider a practical example that they told me about. A pathologist gets a tissue sample. It might be from a person who was just on the operating table.[00:06:13.300] - VivienThe tissue is prepared with chemical stains and then studied. The pathologist interprets what is going on in this tissue. Sometimes pathologists look at many tissue slides from many patients and want to compare them. In other cases, it is information that has to travel quickly to determine how a patient might need to be treated. Or the analysis is for a basic research lab that is studying a particular disease or development. As Patrik Stahl explains, scientists can look at a tissue slide and use stains and dyes to see what is happening there.[00:06:46.630] - VivienWell, sort of. This immunohistochemistry doesn't always answer all the questions of pathologist or other scientists might have[00:06:55.990] - Patrik StåhlSo I think this was like late 2009 and it was Jonas Frisen, who is a who is, s stem cell professor working at Karolinska Institute who is subjected to this kind of immunohistorchemistry a lot during his daily work. And I think that he was the one who first grew tired of a lack of spatial information that they could get out of a stain. And so late 2009, he contacted Joakim Lundeberg and they together in early 2010, initiated this project , trying and then...
In this episode of the Epigenetics Podcast, we caught up with Jason Buenrostro from Harvard University to talk about his work on developing biological tools to measure chromatin dynamics in single-cells. He explains how his lab uses these tools to study chromatin alterations in different cell types and disease states to uncover new mechanisms of gene regulation and their contribution to those diseases. In his first years of his research career Jason Buenrostro took a risk and just added an enzyme called Transposase to cells in a cell culture. What he saw on a subsequent agarose gel astonished him. He was able to recreate a nucleosomal ladder that he knew from experiments using MNase or DNase-Seq, however, without the tedious steps of optimization. In the following years he optimized that method and data analyzation into a method known today as ATAC-Seq. In recent years he was also able to bring ATAC-Seq to the next level and developed single cell ATAC-Seq (scATAC-Seq), and combining it with RNA-Seq in a multi-omics approach. In this Episode we discuss how Jason Buenrostro developed ATAC-Seq in William Greenleaf's lab, how a lack of equipment shaped the ATAC-Seq protocol, and how scATAC-Seq has enabled a whole different way of looking at biological samples. References Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013). Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature Methods, 10(12), 1213–1218. https://doi.org/10.1038/nmeth.2688 Buenrostro, J. D., Wu, B., Litzenburger, U. M., Ruff, D., Gonzales, M. L., Snyder, M. P., Chang, H. Y., & Greenleaf, W. J. (2015). Single-cell chromatin accessibility reveals principles of regulatory variation. Nature, 523(7561), 486–490. https://doi.org/10.1038/nature14590 Buenrostro, J. D., Corces, M. R., Lareau, C. A., Wu, B., Schep, A. N., Aryee, M. J., Majeti, R., Chang, H. Y., & Greenleaf, W. J. (2018). Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation. Cell, 173(6), 1535-1548.e16. https://doi.org/10.1016/j.cell.2018.03.074 Lareau, C. A., Duarte, F. M., Chew, J. G., Kartha, V. K., Burkett, Z. D., Kohlway, A. S., Pokholok, D., Aryee, M. J., Steemers, F. J., Lebofsky, R., & Buenrostro, J. D. (2019). Droplet-based combinatorial indexing for massive-scale single-cell chromatin accessibility. Nature Biotechnology, 37(8), 916–924. https://doi.org/10.1038/s41587-019-0147-6 Related Episodes Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff) Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden) Multiple Challenges in ChIP (Adam Blattler) Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com
Around the world, COVID-19 has been awful. Many, likely millions of people, who have survived their COVID-battle, face a difficult array of symptoms. Breathing problems, joint pain, heart palpitations, brain fog are a few of them. This is part 2 of a three-part podcast series on long-COVID. This episode focuses on brain fog, one of the difficult symptoms of long-COVID. It's a conversation with neuroimmunologist Dr. Avi Nath, who is intramural clinical director of the National Institute for Neurological Disorders and Stroke (NINDS) at the US National Institutes of Health (NIH). There is a story in Nature Methods to go along with this podcast about long-COVID.
COVID-19 has been bad. Many, likely millions of people, who have survived their COVID-battle, face a difficult array of symptoms. Breathing problems, joint pain, heart palpitations, brain fog are a few of them. This is part 1 of a three-part podcast series on long-COVID. You can also find my piece in Nature Methods on long-COVID here. Dr. Nadia Rosenthal, who directs science at the Jackson Laboratory, and her team are working on ways to model this diversity of symptoms, which can help figure out what is amiss in long-COVID and indicate how one might treat it.
COVID-19 has been bad. Many, likely millions of people, who have survived their COVID-battle, face a difficult array of symptoms. Breathing problems, joint pain, heart palpitations, brain fog are a few of them. This is part 3 of a three-part podcast series on long-COVID. This episode is a conversation with Dr. Terina Martinez, a field application scientist at Taconic Biosciences, which develops and sells mouse models. She talks about the challenges and possibilities of modeling long-COVID. There is also an article in Nature Methods to go along with this podcast series.
#14 — You may feel you know Rita Strack (Senior Editor at Nature Methods) already if you follow her engaging and friendly twitter feed (@rita_strack). But here we delve deeper to uncover her very successful academic career involving developing fluorescent proteins and reporters, her love of horses and a passion for Korean food.We find out the type of abuse that editors sometimes face, and how they handle it, how she balances a career and family life, including during a pandemic, and the dangers of pet bunnies. Rita gives her unique perspective on what she thinks was the greatest invention in microscopy, and where the future is headed.Make sure you listen to the end to hear Rita deliver her favourite science joke.Watch or Listen to all episodes of The Microscopists here: https://themicroscopists.bitesizebio.com/
#14 You may feel you know Rita Strack (Senior Editor at Nature Methods) already if you follow her engaging and friendly twitter feed (@rita_strack). But here we delve deeper to uncover her very successful academic career involving developing fluorescent proteins and reporters, her love of horses and a passion for Korean food. We find out the type of abuse that editors sometimes face, and how they handle it, how she balances a career and family life, including during a pandemic, and the dangers of pet bunnies. Rita gives her unique perspective on what she thinks was the greatest invention in microscopy, and where the future is headed. Make sure you listen to the end to hear Rita deliver her favourite science joke. View all episodes of The Microscopists here: https://bitesizebio.com/the-microscopists/
バクテリアで35年前に発見されたレトロンと呼ばれる謎の因子の機能に大胆に迫った論文を読みました。Show notes Bacterial Retrons Function In Anti-Phage Defense. Millman et al Cell 2020…これが今回紹介するレトロンの論文です。 細菌の逆転写酵素およびmsDNAの構造と機能 (日本細菌学雑誌, pdf)…日本語で読めるレトロンの機能などに関する総説論文。 逆転写酵素 (Wikipedia) Genomically encoded analog memory with precise in vivo DNA writing in living cell populations. Science 2014…この論文で初めてレトロンの一部の領域が自在に改変でき、大腸菌の集団に外部刺激を記録するツールとして転用された。 Functional Genetic Variants Revealed by Massively Parallel Precise Genome Editing. Cell 2018…この論文ではレトロンを改造し、相同組み替えのドナーDNAをガイドRNAと同時に細胞へ導入する新しいゲノム編集法として転用された。 RNaseH (Wikipedia) 制限酵素についてはエピソード72で詳しく話しました。 ウイルスプラーク (Wikipedia) バクテリオファージT4とT7 Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies. Nature Methods…Anti-CRISPRタンパク質に関するレビュー論文。 フレームシフト変異 (Wikipedia) RecBCD (Wikipedia) Ediorial notes Defense islandで宝探しをしよう! (soh) レトロンって名前がかっこいい。fugafuga-tronっていう名前に憧れる。イントロン、レトロン、ウルトロン(tadasu)
In this episode we had the pleasure of speaking with Dr. Véronique Kiermer, who is the Chief Scientific Officer at PLOS, the Public Library of Science, where she oversees the Editorial Department and initiatives to promote open science. She trained as a molecular biologist at the University of Brussels and the University of California, San Francisco, and she also worked in the biotech industry in the Bay Area. Veronique started her career in publishing as the founding Chief Editor of Nature Methods, and held several roles at Nature Publishing Group, including the Publisher for Nature Protocols, and executive editor for the Nature journals before moving to PLOS in 2015. We're talking with Veronique about her experience with initiatives that encourage researchers to report method details, code, data, etc. as part of their research output. And you will also get a sneak preview of a new exciting initiative of PLOS in partnership with protocols.io that will be launched in early 2021. Links: Materials Design Analysis Reporting (MDAR) checklist - https://doi.org/10.31222/osf.io/9sm4x PLOS ONE - https://journals.plos.org/plosone/ Show your work. Peer-Reviewed Protocols - https://theplosblog.plos.org/2020/12/show-your-work-peer-reviewed-protocols/
In this episode we had the pleasure of speaking with Dr. Véronique Kiermer, who is the Chief Scientific Officer at PLOS, the Public Library of Science, where she oversees the Editorial department and initiatives to promote open science. She trained as a molecular biologist at the University of Brussels and the University of California, San Francisco, and she also worked in the biotech industry in the Bay Area. Veronique started her career in publishing as the founding Chief Editor of Nature Methods, and held several roles at Nature Publishing Group, including the Publisher for Nature Protocols, and executive editor for the Nature journals before moving to PLOS in 2015. We’re talking with Veronique about her experience with initiatives that encourage researchers to report method details, code, data, etc. as part of their research output. And you will also get a sneak preview of a new exciting initiative of PLOS in partnership with protocols.io that will be launched in early 2021.Links:Materials Design Analysis Reporting (MDAR) checklist - https://doi.org/10.31222/osf.io/9sm4xPLOS ONE - https://journals.plos.org/plosone/
dessanをゲストに迎え、CRISPRの仕組みを利用した様々な技術や遺伝子回路、これからの発展について話しました。Show notes The Nobel Prize in Chemistry 2020…The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing.” Scientifc Background on the Nobel Prize in Chemistry 2020 A TOOL FOR GENOME EDITING…ノーベル財団による詳細なCRISPR研究のレビュー、そしてなぜDoudnaとCharpentierの二人が受賞に値するのかについて説明している。 76. The Chimeric RNA, Researchat.fm…ゲノム編集についてdessanをゲストに迎えて話しました。 A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science 2012…CharpentierとDoudnaによるノーベル賞につながる論文の一つ。CRISPR–Cas9システムがこの論文によってその大枠が明らかにされた。 Multiplex Genome Engineering Using CRISPR/Cas Systems. Science 2013…Feng Zhang labによるヒト細胞におけるゲノム編集技術の報告。 RNA-Guided Human Genome Engineering via Cas9. Science 2012…George Church labによるヒト細胞におけるゲノム編集技術の報告も同時に掲載された。 First rounders: Feng Zhang (Podcast)…Feng Zhangが出演したNatute Biotechnologyのポッドキャスト。おすすめです。 26. Cool tech googlability, Researchat.fm…RNAを標的にできるCas13bについては、エピソード26で紹介しました。 Cas14 (crisp_bio)…“Cas14は、PAMに依存しないssDNA切断活性に加えて、PAMに依存するdsDNA切断活性も帯びている” CasX enzymes comprise a distinct family of RNA-guided genome editors. Nature 2019…CasX Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration. Nature 2019…トランスポゾン型のCasシステムの報告。 RNA-programmed genome editing in human cells. eLife 2013…Doudna labによるヒト細胞におけるゲノム編集技術の報告。FengやChurchらよりも少しだけ遅かった。 Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9. Nature Communications 2014 Ep52. Split into a row Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity. Cell 2013…Double nicking (2つのgRNAとCas9 nickase)によるより正確なゲノム編集方法が示された。 Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 2015…Cas9を用いた転写の活性化手法。 Live visualization of chromatin dynamics with fluorescent TALEs. Nature Structural & Molecular Biology 2013 … TALENを用いた染色体の特定領域のイメージング方法 Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System. Cell 2013…dCas9-EGFPによる生細胞のイメージング技術。SpCas9の場合は、D10AとH840Aの2つの変異を入れることで、DNAに結合するが切断しないdead Cas9 (dCas9)として利用することができる。 Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nature Communications 2017…ガイドRNAにMS2 loopをたくさんつなげることで (14個!)、明るい輝点を得ることができる。 CRISPR-mediated live imaging of genome editing and transcription. Science 2019…こちらは蛍光標識したガイドRNAを利用した生細胞イメージング方法。 A protein tagging system for signal amplification in gene expression and fluorescence imaging. Cell 2014…Sun tagとCas9を用いたイメージング方法。 Split Green Fluorescent Proteins: Scope, Limitations, and Outlook…Split GFP Programmable RNA tracking in Live Cells with CRISPR/Cas9. Cell 2016…PAMmerによるSpCas9のmRNAイメージング CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization. Cell 2018 … CRISPR-GO:CRISPR技術、核内でのゲノム空間構造、ポッドキャスト内ではゲノム同士を寄せるという説明をしていましたが、今調べてみると特定のゲノム領域と核膜やカハール体への再配置ということでした。 Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nature Communications 2017 … こちらがCRISPRの仕組みを用いることで人工的に染色体内部にループを作成した論文。 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 2008 … LacO-LacIの仕組みを用いることでゲノムの特定領域にLacO arrayを差し込み、核膜に局在させたLacIに結合させることである遺伝子領域を核膜側に誘導しようとした論文。最初にこの論文を読んだ時はそのアイデアにたまげました。 9. One-shot beautiful experiment (Researchat.fm)…人工的なDNA領域へ細胞内の情報(細胞系譜)を書き込む技術についてエピソード9で話しました。 CRISPR–Cas encoding of a digital movie into the genomes of a population of living bacteria. Nature 2017…George Churchらは、Cas1-Cas2システムによって馬の動画をバクテリアゲノム書き込み、それを読み出すことに成功した。 Multiplex recording of cellular events over time on CRISPR biological tape. Science 2017…コピー数の異なる2つのプラスミドをCas1-Cas2で取り込ませて、細胞内で人工的な時計のような仕組みを実現した。 Single-Nucleotide-Resolution Computing and Memory in Living Cells. Molecular Cell 2019…Tim Liu Labによる複雑な遺伝子回路の実現。DOMINOについては、プロモーター配列を標的にしているのではなくオペレーター配列でした。 Rewritable multi-event analog recording in bacterial and mammalian cells. Science 2018…David Liu labから報告されたガイドRNAによって連鎖する遺伝子回路(カスケード)の実現。 Terminal Deoxynucleotidyl Transferase, TdT…テンプレートに依存しないDNA合成を可能にする酵素。 Tandem fluorescent protein timers for in vivo analysis of protein dynamics. Nature Biotechnology 2012…GFP Timer Permanent genetic memory with >1-byte capacity. Nature Methods 2014 Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Science 2016…自分で自分のガイドRNAを編集することで、理論的には無限に情報を書き込む方法が提案されたが、領域が壊れてしまう問題もある。 Ten Simple Rules to Win a Nobel Prize. ヘンリー・ブラッグ (Wikipedia) iPS細胞 (Wikipedia) 国境なき医師団 Human Genome Project Xiaowei Zhuang Expansion microscopy (Wikipedia) Renato Dulbecco (Wikipedia) Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nature Biotechnology 2019…LEAPER crisp_bio … 世界広しといえでも、これだけCRISPRの最新情報がまとまっているサイトはCRISP_BIOさんの他に世の中には存在しません。日本語でCRISPRの最先端情報を追える喜び。CRISP_BIOさん、いつもありがとうございます。 Editorial notes 1分でわかるとか無理なのですが、一方で言葉を尽くせばわかる可能性についても同時に信じておりますので…(soh) 思い出しながらどんどん話しているので、後から聞き返すと細部が間違っていたりしています。気になった方はshow notesをご参照ください。(dessan) いい感じのグルーヴがみられてよかったです。ポッドキャストやってきてよかったです。(tadasu) 最初に喋らんと出番が無くなる!と思ってこれまでの流れをまとめてみたんですが細かく色々ミスってました…(coela)
Se houbese un tratamento eficaz contra a Covid e fose creado utilizando experimentación con ratos de laboratorio habería que prohibilo? Isto non é unha ficción, unha recomendación da Unión Europea veta a creación de anticorpos monoclonais empregando estes animais. Hai proxectos que corren o risco de paralizarse. Esta semana unha carta en Nature Methods alerta que na actualidade non existen alternativas viables para a creación destes anticorpos de alta especifidade que teñan como obxecto curar doenzas en humanos. Un exemplo da utilidade destas investigacións é o tratamento que ven de recibir Donald Trump. Conversamos con África González sobre anticorpos monoclonais, e tamén sobre os novos test de antíxenos. www.efervesciencia.org
Se houbese un tratamento eficaz contra a Covid e fose creado utilizando experimentación con ratos de laboratorio habería que prohibilo? Isto non é unha ficción, unha recomendación da Unión Europea veta a creación de anticorpos monoclonais empregando estes animais. Hai proxectos que corren o risco de paralizarse. Esta semana unha carta en Nature Methods alerta que na actualidade non existen alternativas viables para a creación destes anticorpos de alta especifidade que teñan como obxecto curar doenzas en humanos. Un exemplo da utilidade destas investigacións é o tratamento que ven de recibir Donald Trump. Conversamos con África González sobre anticorpos monoclonais, e tamén sobre os novos test de antíxenos. www.efervesciencia.org
(2:08) A reprogramación de células adultas en células nai pluripotentes inducidas (iPSC) é unha realidade actual. Pero o proceso ten moi baixa eficiencia e mesmo pode dar lugar a tumores benignos nas células. Unha investigación dos grupos dos grupos de Epitranscriptómica e Envellecemento e de Células Nai e Enfermidades Humanas do CiMUS veñen de ganar o Premio de Investigación 2020 da Real Academia Galega de Ciencias por un artigo en Cell Stem Cell. Nel os investigadores dan conta do mecanismo dun esencial para estas transformacións. Conversamos co investigador de doutoramento Alejandro Fuentes. (14:10) Se houbese un tratamento eficaz contra a Covid e fose creado utilizando experimentación con ratos de laboratorio habería que prohibilo? Isto non é unha ficción, unha recomendación da Unión Europea veta a creación de anticorpos monoclonais empregando estes animais. Hai proxectos que corren o risco de paralizarse. Esta semana unha carta en Nature Methods alerta que na actualidade non existen alternativas viables para a creación destes anticorpos de alta especifidade que teñan como obxecto curar doenzas en humanos. Un exemplo da utilidade destas investigacións é o tratamento que ven de recibir Donald Trump. Conversamos con África González sobre anticorpos monoclonais, e tamén sobre os novos test de antíxenos. (38:08) Beatriz Díaz preséntanos a segunda edición dos Zendal Awards (40:27) O fósforo é un elemento escaso nas estrelas. Unha investigación do Instituto Astrofísico de Canarias en colaboración co CIT da Universidade da Coruña atopou un pequeno grupo de estrelas na nosa galaxia cunha abundancia de fósforo que cuestiona os mecanismos de nucleosíntese actuais. Conversamos con Raúl Santoveña que gañou o premio de investigadores mozos da RAGC por este traballo que se publicou en Nature Communications. www.efervesciencia.org
(2:08) A reprogramación de células adultas en células nai pluripotentes inducidas (iPSC) é unha realidade actual. Pero o proceso ten moi baixa eficiencia e mesmo pode dar lugar a tumores benignos nas células. Unha investigación dos grupos dos grupos de Epitranscriptómica e Envellecemento e de Células Nai e Enfermidades Humanas do CiMUS veñen de ganar o Premio de Investigación 2020 da Real Academia Galega de Ciencias por un artigo en Cell Stem Cell. Nel os investigadores dan conta do mecanismo dun esencial para estas transformacións. Conversamos co investigador de doutoramento Alejandro Fuentes. (14:10) Se houbese un tratamento eficaz contra a Covid e fose creado utilizando experimentación con ratos de laboratorio habería que prohibilo? Isto non é unha ficción, unha recomendación da Unión Europea veta a creación de anticorpos monoclonais empregando estes animais. Hai proxectos que corren o risco de paralizarse. Esta semana unha carta en Nature Methods alerta que na actualidade non existen alternativas viables para a creación destes anticorpos de alta especifidade que teñan como obxecto curar doenzas en humanos. Un exemplo da utilidade destas investigacións é o tratamento que ven de recibir Donald Trump. Conversamos con África González sobre anticorpos monoclonais, e tamén sobre os novos test de antíxenos. (38:08) Beatriz Díaz preséntanos a segunda edición dos Zendal Awards (40:27) O fósforo é un elemento escaso nas estrelas. Unha investigación do Instituto Astrofísico de Canarias en colaboración co CIT da Universidade da Coruña atopou un pequeno grupo de estrelas na nosa galaxia cunha abundancia de fósforo que cuestiona os mecanismos de nucleosíntese actuais. Conversamos con Raúl Santoveña que gañou o premio de investigadores mozos da RAGC por este traballo que se publicou en Nature Communications. www.efervesciencia.org
RNA分子の局在を一斉に捉えるイメージング技術とそれをささえる巧妙な方法について原著論文を解説しました。Show notes elmo囲い 電王戦 Single-cell in situ RNA profiling by sequential hybridization. Lubeck et al Nature Methods 2014…CaiらによるSeqFISHのオリジナル論文。無料で読めます。 Ep16. Beyond imaging (Researchat.fm)…エピソード16回ではイメージングせずに位置情報を再構成するDNA Microscopyについて解説しています。 WHAT IS SEQFISH?…CaiらによるSeqFISH技術紹介のページ。とてもわかり易いです。 Spatially resolved, highly multiplexed RNA profiling in single cells. Chen et al Science 2015…MARFISHのオリジナル論文。こちらも無料で読めます。 パリティビットの意味と誤り検出、誤り訂正の方法…誤り訂正に関する解説。 ハミング符号 : データの誤り検知/訂正をインタラクティブに学ぶ…MARFISHのプローブの設計において用いられた誤り訂正符号の一つ。 Researchat.fm お便りフォーム…Researchat.fmではリスナーの方からのお便りを募集中です。よろしくお願いします。 無能なナナ…おすすめマンガ JAPAN PODCAST AWARDS Editorial notes うまく解説できたか心配ですが、興味があるひとはこれを取っ掛かりに論文にもチャレンジするのもよいかもしれません (soh) RNAの局在は非常に興味深いテーマですね、めっちゃ勉強になりました (coela) Coela先輩は本当に意識が高いんですね。すばらしいスピーチでした (tadasu)
DNA microscopy法という分子や細胞の位置を、分子間の近接情報のみから再構成することができる新しい方法論について、原著論文とその周辺技術を中心に詳しく話しました。Show notes DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction…bioRixv (Open Acess) 論文のPDFが入手できます。 DNA Microscopy論文のFigure 1…PodcastではほぼFigure1の説明に終始しているので、これを見ながら…だと理解の助けになるのかもしれない… DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction…Cell Press. Joshua Weinsteinのセミナー動画 (YouTube)…1st author Joshua Weinsteinが論文には書かれていない背景なども含めてDNA microscopyについてBroad研で発表した動画。 dnamic (GitHub)…DNA microscopyのデータ解析に使われたpythonのコード In-gel PCR…Four-arm PEG acrylateとHS-PEG-SHというポリエチレングリコール (PEG)をPCR反応液に追加することにより、高温下でも分子の拡散を抑えることができる。この液体の中で、Overlap extension PCRが起き、それぞれのUMIは新しいタグを持ちながら増幅され、近接する2つのUMIを持つ分子同士はUEIを受け取りつつ連結される。 Overlapping extension PCR Virtual microfluidics for digital quantification and single-cell sequencing. Nature Methods 2016…In-gel PCRの元論文。 In situ cDNA synthesis…固定した細胞に対しても逆転写酵素とプライマーなどを用いてcDNA合成を行うことができる。これを利用することで、細胞内でRNA分子の配列をその場でシーケンシングすることがIn situ RNA sequencing (FISSEQ法)で可能になった。 Fluorescent In Situ Sequencing (FISSEQ) Illumina sequencing…一塩基ごとに蛍光標識されたdyeを用いた伸長反応により大量のDNA配列を決定する。こちらのYoutubeの動画が原理を知るにはわかりやすい。 A Theory of Network Localization A remark on global positioning from local distances… Locally rigid embeddingのオリジナル論文。 ブラウン運動…何故、あるUMIを持つDNAが溶液中を移動して、異なるUMIを持つDNAと出会い、Overlap extension PCRを介して、新たなUEIを形成することができるのか。DNA microsocpyで明らかにしようとしている空間サイズでは、PCRに用いられるような高温にしてしまうと、一瞬でDNA群は均一に混じり合ってしまうことが予想されるが、粘度が高いゲル中でPCR反応を行うことにより、DNA分子の拡散を抑えることができる。これにより、UMI diffusion cloudsが形成される。 距離空間 (Wikipedia) 正規分布 (Wikipedia) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Lieberman-Aiden et al. Science, 2009…Hi-C法のオリジナル論文。この論文を起点として、核内における染色体高次構造、クロマチン構造解析が爆発的に進むようになった。この方法も光学系ではなく、シーケンシングによってクロマチン構造を明らかにしようというコンセプトからなる。DNA配列同士の”Contact Probability”を中心にしている。 光学顕微鏡の解像度の限界:回折限界…蛍光顕微鏡を用いる際の回折限界は、波長の大きさとレンズの開口数によって計算することができる。 超解像顕微鏡法…2014年に超解像顕微鏡法がノーベル賞を受賞したときに書かれた阪大永井先生の総説。超解像顕微鏡法とは回折限界以下で行うことができる蛍光イメージングのことを指す。PALM, STORM, STED, SIMなど様々な方法が現在用いられている。 ハウスキーピング遺伝子…どの細胞においても定常的に多量発現している遺伝子のこと。GAPDH(glyceraldehyde-3-phosphate dehydrogenase)、β-アクチンなどが含まれる。DNA microscopy法でもbeaconとしてACTBやGAPDHが用いられた。 V(D)J recombination (Wikipedia)…B細胞やT細胞ではランダムな遺伝子群の組み換え反応 (recombination)により、ウィルスやがん細胞など多様な抗原に作用する抗体が作り出される。 smFISH…蛍光標識した蛍光プローブを用いることで一分子のRNAの位置を調べることができる。 MS2 tagging (Wikipedia)…MS2 RNAとそれに結合するMCPタンパク質を組み合わせることで生細胞で特定のRNAを可視化することができる。 CLARITY (Wikipedia)…厚みのある組織の透明化技術の一つ。 DNA Microscopyのsohによるメモ Editorial notes Cell誌のTheoryセクションということもあり、日本ではほとんど報道もなく紹介記事も見当たらない中、このDNA microscopyという画期的なコンセプトが伝わればいいと思いますが果たして…(soh) カンゼンニリカイシタ (coela) トリッキーな内容と論文の文体から、とてもスマートに感じるDNA microscopyであるが、内容を理解していくにつれて、案外膨大な試行の先にたどり着いた泥臭い方法論なのではないかと思うようになった。枯れたテクノロジーをできるだけ使いたい保守派研究者としては、DNA microscopyに対して思うことはたくさんある。しかし、そのモヤモヤは一度横に置き、自分の研究にどのように応用できるか、そしてこれからのどのように発展するか、その行き先を見つめていきたい (tadasu)
It's the December episode of 3-Minute 3Rs, brought to you by , the NC3Rs (www.nc3rs.org.uk), the North American 3Rs Collaborative (www.na3rsc.org) and Lab Animal (www.nature.com/laban) The papers behind the pod: 1. Optimizing the design of population-based patient-derived tumor xenograft studies to better predict clinical response https://bit.ly/2GwGJ7N 2. An In Vitro Model of Hematotoxicity https://bit.ly/2Ezgaw3 3. Found In Translation https://go.nature.com/2UVJ0g6 [NC3Rs] Every cancerous tumor is different and treating two tumors with the same drug may result in two very different outcomes, which contributes to the high failure rate during cancer drug discovery. One experiment type gaining interest to model this tumor heterogeneity is screening a population of patient-derived tumor xenograft models, or PDX models. However, there is little guidance available for these experiments. This risks poor experimental design that could result in a study being under or overpowered. Both these scenarios waste animals. A new freely available interactive tool from a team at AstraZeneca, published in Disease Models & Mechanisms, enables scientists to design robust and reproducible population PDX studies. The tool developed by Floc'h et al explores the design of population PDX studies and how this can impact the risk of both false-negative and false-positive results. Each experiment for a specific drug or cancer type is unique so the tool cannot provide exact recommendations, but what it can do is support you in selecting the optimal design for your experiment whilst ensuring the 3Rs are also considered. Details for how to access the tool can be found via the link in the description. [NA3RsC] Mature blood cells and bone marrow are common targets of drug toxicity. In addition to leading to significant complications for patients receiving antineoplastic agents for cancer treatment, these hematotoxic effects can be limiting, preventing administration of the doses needed for therapeutic efficacy. Screening for potential toxicity to the hematopoietic system in animals and in human cell-based in vitro approaches is critical in early drug development. The CFU assay has been validated as the traditional screen for hematotoxicity, but has limitations. A publication in Current Protocols in Toxicology by Mahalingaiah and colleagues describes the next-generation, high-throughput assay as a refined approach. A liquid culture, lineage-specific, in vitro cell differentiation model offers multiple advantages over the traditional assay, making it a versatile and useful tool to screen compounds. In addition to decreasing the number of animals required for hematoxicity determination, this human, cell-based in vitro assay is a useful alternative to in vivo studies for investigative work in understanding mechanisms of lineage-specific hematotoxicity at different stages of differentiation. [LA] So you've made a mouse model of disease, applied a treatment, and measured gene expression. Now what? You might think the gene with the greatest changes in expression is going to be the most important for the disease. But there's a pretty big evolutionary gap between mouse and man. From just your experiment, do you really know how relevant that gene will be? To better bridge the species gap, researchers from Technion have developed a new statistical model that takes decades of previously recorded gene expression data in mouse and human into account. They call it Found in Translation, or FIT for short. For new mouse data, FIT calculates a per-gene effect size and predicts which gene in your mouse might be most relevant to humans. It can potentially rescue genes that might not otherwise make the cut for further studies and de-prioritize those important to a mouse but perhaps less so to a person. No new mice experiments required. You can find all the details about FIT in Nature Methods, and you can try it out yourself with your own gene expression data at mouse2man.org. See acast.com/privacy for privacy and opt-out information.
For the past few years, a new scientific tool known as CRISPR-Cas9 has been hailed as the future of medicine. But a new study, published in Nature Methods , found that using CRISPR-Cas9 to edit a genome can result in hundreds of unintended mutations being introduced. Is this tool still the future, or should we slow down and pump the brakes on gene editing? Jeff and Anthony discuss. GET BONUS EPISODES, VIDEO HANGOUTS AND MORE. VISIT: http://patreon.com/wehaveconcerns Get all your sweet We Have Concerns merch by swinging by http://wehaveconcerns.com/shop Hey! If you’re enjoying the show, please take a moment to rate/review it on whatever service you use to listen. Here’s the iTunes link: http://bit.ly/wehaveconcerns And here’s the Stitcher link: http://bit.ly/stitcherwhconcerns Or, you can send us mail! Our address: We Have Concerns c/o WORLD CRIME LEAGUE 1920 Hillhurst Ave #425 Los Angeles, CA 90027-2706 Jeff on Twitter: http://twitter.com/jeffcannata Anthony on Twitter: http://twitter.com/acarboni Today’s story was sent in by Zach Erbaugh: http://www.newsweek.com/unexpected-mutations-new-gene-editing-technology-crispr-618235?spMailingID=1914531 If you’ve seen a story you think belongs on the show, send it to wehaveconcernsshow@gmail.com, post in on our Facebook Group https://www.facebook.com/groups/WeHaveConcerns/ or leave it on the subreddit:http://reddit.com/r/wehaveconcerns
When it comes toCrispr, the bacterial wünderenzyme that allows scientists to precisely edit DNA, no news is too small to stir up some drama. On Tuesday morning, doctors from Columbia, Stanford, and the University of Iowa published a one-page letterto the editor of Nature Methods—an obscure but high-profile journal—describing something downright peculiar.
Living cells and organisms often suffer from the high light intensities that are used in conventional imaging. Light sheet microscopy reduces phototoxic effects and bleaching, by only illuminating a specimen in a single plane at a time whilst the signal is detected in a perpendicular direction. In combination with high-speed cameras for image acquisition, light sheet microscopy is a very gentle method to observe fast biological processes in sensitive organisms over an extended time period. By moving the sample along this plane, specimens are optically sectioned and imaged in 3D. These exciting possibilities led Nature Methods to cite light sheet imaging as their Method of the Year for 2014. Learn more at http://bitesizebio.com/webinar/24339/the-best-of-both-worlds-combining-light-sheet-and-confocal-microscopy/
Bam.iobio is the first app of its kind that allows scientists to analyze genome sequence data on their web browser, interactively, and in real-time, without having to rely on terabytes of storage and vast sources of computing power. The resource, developed by a team led by Gabor Marth, DSc, co-director of the USTAR Center for Genetic Discovery and human genetics professor at the University of Utah, was published in the journal Nature Methods on Nov. 25. Marth explains bam.iobio, its features, another ready-to-use app – vcf.iobio - for analyzing variant call format files, and plans to allow developers to build off the IOBIO operating system. Learn more about bam.iobio.
June 02, 2011 In this seventh episode of "This Week in Pediatric Oncology" TWiPO podcast, host Dr. Tim Cripe interviews Dr. E. Anders Kolb and Dr. Andrew Napper from Nemours in Wilmington, Delaware. This informative discussion covers the strategies, scope, and challenges of target discovery, drug development, and preclinical testing for pediatric cancers, a complex process that has been accelerated by high throughput screening technology that has only recently become available in academic settings. Dr. Kolb is the Director of Blood and Bone Marrow Transplantation at Alfred I. duPont Hospital for Children, and Head of the Cancer Therapeutics Laboratory at Nemours Biomedical Research. He is also a Principal Investigator in the Pediatric Preclinical Testing Program (PPTP), a comprehensive program to systematically evaluate new agents against childhood solid tumor and leukemia models. Dr. Andrew Napper joined the research team at the Nemours Center for Childhood Cancer Research (NCCCR) in 2009 to establish its High Throughput Screening and Drug Discovery Laboratory. Dr. Napper came to Nemours from the University of Pennsylvania, where he was the Director of High Throughput Screening for the Penn Center for Molecular Discovery, one of the original ten centers established as part of the National Institutes of Health’s Roadmap initiative to discover drugs for neglected diseases. For more information on this program and technology: Lab Offer Hope for Kids with Cancer, Wilmington News Journal (8/24/09) Academic screening goes high-throughput, Nature Methods 7, 787–792 (2010) Please send questions and comments to twipo@solvingkidscancer.org
Recent research has found that mice make humanlike facial expressions when they are in pain. Christie Nicholson reports