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Craig Walsh, the Regional Director for Eastern Canada with the United Food and Commercial Workers Union, speaks with us about the workers at the Covered Bridge Potato Chip factory who've lost their jobs after the plant burned down. We hear your feedback on cell phones in schools. And on the phone-in: What's the best way to regulate coastal development? Our guests are Patricia Manuel and Don Jardine.
Welcome to the last Startup Dad episode of 2023! It has been one hell of a year. Starting in June I released a show a week for the entire rest of the year; 27 episodes in total. Talking parenthood with dozens of startup dads and a few startup moms blew away all of my expectations. For this episode I pulled together the best of over two dozen conversations covering everything from mistakes made to frameworks for parenting success. At the end I asked many of my guests what they're most looking forward to in 2024. This episode includes excerpts from nearly every one of my conversations. Guests include: Nick Soman, Buster Benson, George Arison, Guy Yalif, Jake Wood, Gaurav Vohra, Tobi Emonts-Holley, Ben Williams, Lloyed Lobo, Ryan Johnson, Mike Duboe, Sara and Eric Mauskopf, Trae and Michelle Stephens, Aaron Huey, Will Rocklin, Tom Willerer, Darius Contractor, Adam Grenier, Alex Cohen, Brian Balfour, Josh Herzig-Marx and Carla Naumburg, Casey Woo, Fareed Mosavat, and Matt Greenberg. In this episode we discuss: Mistakes made as a Dad The successes and high points of parenting Frustrations and challenges with parenting Frameworks for success Advocacy and raising children with special needs Coping with loss Startup Dads' optimism for 2024 Where to find Adam Fishman - Newsletter: https://www.fishmanafnewsletter.com - Newsletter: http://startupdadpod.substack.com - LinkedIn: https://www.linkedin.com/in/adamjfishman/ - Twitter / X: https://twitter.com/fishmanaf - Instagram: https://www.instagram.com/startupdadpod/ — In this episode, we cover: [0:00] Hello & intro from Adam [01:15] Mistakes made as a parent [01:22] Ryan Johnson (CPO, CallRail) - thinking your kids are older than they are [02:41] Tobi Emonts-Holley (CEO, Tiphereth) - losing your temper, recovering and learning to let go [04:20] Nick Soman (CEO/founder, Decent) - when I felt like I was drowning [05:45] Mike Duboe (General Partner, Greylock) - being too hard on yourself [07:12] Lloyed Lobo (Co-founder, Boast.ai) - yelling at your kids [07:54] Jake Wood (Founder, Groundswell and Team Rubicon) - avoiding mistakes of the heart [08:42] Guy Yalif (Co-founder/CEO, Intellimize) - quality minutes with your kids vs. quantity of hours [09:29] Gaurav Vohra (Founding team, Superhuman) - taking advice from other parents; not getting a crib [11:50] Buster Benson (Product leader, Medium) - thinking your kids are more mature than they are [14:27] George Arison (CEO, Grindr) - not explaining why to kids [14:46] Ben Williams (PLG Advisor, PLGeek) - thinking it would be easy [15:15] Parenting successes [15:24] Will Rocklin (Product Advisor) - marriage and parenthood unlocking your best self [17:25] Tom Willerer (COO, Reforge) - watching your kids be successful [21:51] Trae and Michelle Stephens (Partner, Founders Fund, Co-founder Anduril, Co-founder Oathcare) - watching kids learning new things and experiencing the world [22:53] Eric and Sara Mauskopf (Product leader, Winnie; CEO/co-founder, Winnie) - rejoining the workforce and working with your spouse [027:20] Guy Yalif - seeing your kids navigate transitions; college and high school [28:06] Darius Contractor (CGO, Otter.ai) - helping your kids be centered and defining success with them [28:59] George Arison - watching your kids learning [29:28] Aaron Huey (Founder, National Geographic Photographer, 3rd Coolest Dad in America) - being named the 3rd coolest Dad in America [31:07] Parenting frustrations and challenges [31:19] Will Rocklin - conception struggles and a positive experience with IVF [33:23] Alex Cohen (Product leader, Carbon Health) - not having family or a support network nearby [34:25] Nick Soman - starting a company and becoming a husband and father at the same time [35:13] Eric and Sara Mauskopf - navigating cancer; a dismembering experience; family planning with cancer [42:28] Adam Grenier (VP Growth, Eventbrite) - having a child with special needs [44:17] Buster Benson - navigating separation and divorce; talking to your kids about it; advice for others [53:03] Tobi Emonts-Holley - getting intense feedback online and saying the wrong thing [01:00:20] Best parenting frameworks [01:00:30] Nick Soman - irrevocable guidelines [01:00:59] Tobi Emonts-Holley - personal discipline equals freedom [01:02:57] Mike Duboe - making time for date night [01:04:04] Lloyed Lobo - positive discipline, rewarding the effort and trusting the process [01:07:51] Jake Wood - making sure your kids know they're loved [01:08:30] Guy Yalif - making sure your kids know they're loved and you only control how you show up [01:09:29] Adam Grenier - tools from Brene Brown and understanding your couple capacity [01:10:37] Gaurav Vohra - Delete, automate, delegate [01:13:14] Casey Woo - the importance of routine [01:13:50] Josh Herzig-Marx and Carla Naumburg (Product advisor, best-selling author) - prioritization and tradeoffs using mission and vision [01:19:04] Buster Benson - creating a safe space and not trying to diagnose your kids [01:21:37] Adam Grenier - special time with each kid [01:22:50] Gaurav Vohra - full vertical responsibility management [01:28:41] Brian Balfour (CEO/founder, Reforge) - defining your parenting values [01:30:15] Ben Williams - making 1-on-1 time [01:31:37] Alex Cohen - giving zero fucks and going with the flow [01:32:15] Fareed Mosavat (Advisor) - remembering that you're the adult [01:33:06] Advocating for your kids [01:33:17] Ryan Johnson - getting difficult medical diagnoses and navigating that process [01:36:07] Matt Greenberg (CTO, Handshake) - the process of diagnosing and advocating for your autistic child in the school system [01:41:29] Adam Grenier - the tools for helping and advocating for your autistic child with caregivers [1:46:01] Ben Williams - helping your child understand racism [1:47:14] George Arison - navigating the surrogacy process as a gay man [1:54:41] Matt Greenberg - more about advocating for your autistic child [1:59:51] Startup dads & moms discuss loss [2:00:02] Trae & Michelle Stephens - navigating miscarriage and advice for others [2:02:24] Brian Balfour - coping with the loss of a child at birth [2:08:06] Lloyd Lobo - navigating the loss of a twin [2:13:21] What are Startup Dads looking forward to in 2024? [2:13:29] Matt Greenberg - looking forward to his four year old turning five [2:13:47] Lloyd Lobo - my wife's 40th birthday [2:14:13] Alex Cohen - side projects turning into real things [2:14:48] George Arison - excited about building culture together and the transition to kindergarten [2:15:58] Gaurav Vohra - traveling to exciting places as a family [2:17:06] Ben Williams - taking a family holiday... somewhere warm [2:18:05] Trae & Michelle Stephens - having an escape from the city, celebrating milestone birthdays, and rest [2:19:13] Tobi Emonts-Holley - watching his kids pursue their sports and passions; connecting with more dads [2:20:19] Ryan Johnson - the technology landscape settling and what will happen with AI [2:21:36] Will Rocklin - a baby who sleeps [2:22:39] Thank you — Show references: IVF - https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716 RMA - https://rmanetwork.com/ Harville Hendrix - https://harvilleandhelen.com/ Fatherly - https://www.fatherly.com/ National Geographic - https://www.nationalgeographic.com/ UCSF Fertility Clinic - https://crh.ucsf.edu/ Jocko Willink - https://jocko.com/ The Score Takes Care of Itself: My Philosophy of Leadership by Bill Walsh, Steve Jamison & Craig Walsh - https://www.amazon.com/Score-Takes-Care-Itself-Philosophy/dp/1591843472 Brene Brown - https://brenebrown.com/ Fair Play by Eve Rodsky - https://www.amazon.com/Fair-Play-Game-Changing-Solution-When/dp/0525541934 The Seven Principles For Making Marriage Work by John M. Gottman PHD - https://www.amazon.com/Seven-Principles-Making-Marriage-Work/dp/0553447718 Brickies - https://brickies.club/ CCRM Fertility - https://www.ccrmivf.com/ HAND of Bay Area - https://handsupport.org/ — Production support for Startup Dad is provided by Tommy Harron at http://www.armaziproductions.com/ Episode art designed by Matt Sutherland at https://www.mspnw.com/
“I had one job, which was to get the data right. Why was that so freaking hard?” asked Barr Moses, co-founder and CEO of Monte Carlo, the world's first data observability platform, discussing what motivated her to create the product. Having worked with data for 15 years, she realized so many people across the industry couldn't seem to get it right, nor did they have a systematic, scalable way to make sure data was accurate. In the world we're living in, where so many people have access to data, just a few minutes of inaccurate data can lead to poor customer experience and millions of dollars in lost revenue. It's a problem Barr says will only get worse over time, as data becomes more important to infrastructure. Barr explains what it was like to create a whole new category, something from nothing, even when some people were telling her it would never work and that she was throwing her career away. She knew there was a company to be built there, and she wanted to be the one to do it and be proud of the journey along the way—which she admits is a lot of hard work. Category creation is really solving customer problems, and in so doing, the customer becomes co-creator of the category because they have the answers. Customer happiness is at the heart of the whole operation. Barr expands upon this and other codified values that make up the foundation of Monte Carlo. Barr reveals what the two main rules any business should have, from the beginning and forever. Find out why it's important that people around you pass “The Mom Test,” what the odds are that data will ever be 100% accurate, and what it's like to be married to your co-founder. Quotes: “The idea of data being wrong would get a really strong reaction. It resonated. I think that was the first ‘aha' moment. People that I didn't even know would say, ‘Hell, yes, I have that problem, please help me solve it now. So that was the very first lightbulb moment.” (9:52-10:17 | Barr) “We're not looking for someone to say, ‘Hey we have 100 percent confidence.' We're looking for someone to say, ‘Hey, this data is important enough for us to invest something in making sure that it's accurate.' It's about treating the issue with the diligence it deserves." (15:53-16:07 | Barr) “Think about application reliability: A couple of decades ago, nobody cared if your app was up or down. But then Netflix is down for 45 minutes in 2016 because of duplicate data. Netflix being down is a hell of a problem.” (16:07-16:26 | Barr) “Customers don't give a shit about you creating a new category or not. They literally don't care. They care about, ‘Are you solving a real problem for me?' Helping people and solving their problem is way more important.” (32:58-33:20 | Barr) “Our measure of success isn't years or weeks, it's literally minutes. Every minute that you're spending on something should be high-value.” (39:50-40:00 | Barr) Connect with Brendan Dell: LinkedIn: https://www.linkedin.com/in/brendandell/ YouTube: https://www.youtube.com/c/BrendanDell Instagram: @thebrendandell TikTok: @brendandell39 Buy a copy of Brendan's Book, The 12 Immutable Laws of High-Impact Messaging: https://www.indiebound.org/book/9780578210926 Connect with Barr Moses: LinkedIn: @barrmoses barr@montecarlodata.com Check out Barr Moses recommended books: The Mom Test by Rob Fitzpatrick https://www.indiebound.org/search/book?keys=The+Mom+Test Daring Greatly: How the Courage to Be Vulnerable Transforms the Way We Live, Love, Parent, and Lead by Brene Brown https://www.indiebound.org/book/9781592408412 The Score Takes Care of Itself by Bill Walsh, Steve Jamison and Craig Walsh https://www.indiebound.org/book/9781591843474 Please don't forget to rate, comment, and subscribe to Billion Dollar Tech on Apple, Spotify, or wherever you listen to podcasts! Use code Brendan30 for 30% off your annual membership with RiverSide.fm Podcast production and show notes provided by HiveCast.fm
Craig Walsh, installation artist, on using image projection, or projection mapping, to animate the natural world, provide an engaging interactive experience and bring a forest to life with living faces. Recorded last year at WOMADelaide, before the global pandemic really hit.
I wanted to share a few stories with some lessons I've learned about public speaking and beating the fear. I thought it would be better done as a conversation so for this episode I am being interviewed by guest interviewer, Craig Walsh. Some of the things we cover include managing a pre-speaking anxiety attack, the question of content vs skill & technique, the secret to being a good event MC, and how I got my very first coaching client.
As far as tough policing goes, Craig Walsh has done it all. He worked in Homicide, the Armed Robbery Squad and the Special Operations Group, better known as a SWAT team. In doing so he's been pitched up against some of Victoria's most violent criminals in a full array of cases from shootings to sieges. But like many of his fellow officers, the job would eventually take a toll on Craig's mental health. Hosted on Acast. See acast.com/privacy for more information.
As far as tough policing goes, Craig Walsh has done it all. He worked in Homicide, the Armed Robbery Squad and the Special Operations Group, better known as a SWAT team. In doing so he’s been pitched up against some of Victoria’s most violent criminals in a full array of cases from shootings to sieges. But like many of his fellow officers, the job would eventually take a toll on Craig’s mental health.
Join Ben Reid and Claire Parkes from Ian Reid Buyer and Vendor advocates and host Jane Nield for a weekly look at the real estate market.This podcast is made possible by our sponsors thanks to Red Energy. Moving is hard but switching your electricity and gas is easy. Call Red Energy on 131 806 or visit their website HERE.This week we discuss the impact that Stage 3 COVID-19 restrictions have and will have on sellers and buyers, and how a buyer or vendor advocate can help you to sidestep some of the stress of selling or buying. Moving house can be stressful - so this week we also chat with Helen Vassiliou and Craig Walsh from Direct Connect to find out how they can ease more of the moving stress for you. To get in touch with the Melbourne based team at Direct Connect visit their website HERE or give them a call on 1300 664 715.You can contact Ben via email ben@ianreid.com.au and contact Claire via claire@ianreid.com.au or check out the Ian Reid website HERE.You can download Ian Reid's free booklet Fatal Real Estate Traps Exposed - which you can download HERE.This podcast is produced by Ben Reid and Claire Parkes and engineered and edited by Jane Nield for Crocmedia.
Pedro Sorrentino and his team were successful angel investors with multiple exits and technology executives and entrepreneurs when Pedro and his team decided to co-found ONEVC, a cross-border seed-stage firm based in San Francisco and São Paulo. He went from being a tech executive to starting his own company and then transitioned into angel investing and parlayed this successful track record into a $38M venture capital fund. ONEVC’s cross-border vision means that they invest in Latin America and the US with very specific theses for both regions. The fund focuses on investing early into category-defining startups that operate in Latin America or startups outside of Silicon Valley, whether that be in Latin America, US or in Europe, that have the potential to go global. In this episode, we cover the ONEVC investment thesis, and why they decided to invest against this thesis. We also discuss how Pedro thinks about helping companies he partners with and his advice to startup founders going into the Brazilian market. Lastly, we talk about how Latin America’s ecosystem is changing, advice to founders seeking funding from VCs, and advice Pedro would give to his younger self when he was first starting ONEVC. “We are in the business of partnering with inevitability” Pedro says that with seed and pre-seed investments it’s only clear that it’s going to work after the fact. Some startups look really promising at the moment of investment, but may lose momentum for different reasons after receiving the funds. Others are an unstoppable brute force of nature; these are what Pedro calls ‘the inevitables’. Gaining access to a fund’s capital and time will only speed up the current trajectory of these types of founders. Find out how Pedro thinks about ONEVC’s framework for finding investments that will create returns in this episode of Crossing Borders. How ONEVC helps its portfolio companies Pedro and ONEVC try to support companies as much as they can, trying to get heavily involved with their portfolio companies. Investing means helping their portfolio companies in three key areas: raising capital, providing access to top candidates when recruiting, and assisting in sales. Pedro explains that at ONEVC they believe they need to earn their place in cap tables by helping in these three areas. Learn more about ONEVC’s investment strategies in this episode of Crossing Borders. Advice to Spanish-speaking founders in the Brazilian Market Pedro admits that despite Brazil’s friendly reputation, it can be a very hostile environment for doing business. He advises foreign founders to find a local partner to help introduce them to the best lawyers, accountants, and service providers when opening the Brazilian market. Pedro also suggests that building a corporate culture that can permeate both national and language barriers is key to developing a scalable business in a systematic way, as well as to attract Brazil’s top talent. Tune in to this episode of Crossing Borders to hear more advice on pursuing the Brazilian market as a Spanish-speaking founder. From starting companies to eventually investing in them, Pedro Sorrentino has had a long trajectory in the US and Latin American startup ecosystems. Today, as founder of ONEVC, he invests in companies like Rappi, Pipefy, and Loggi and helps them unleash their full potential in their respective markets. Show Notes: [01:45] - About ONEVC, past and present [05:10] - ONEVC’s investment parametres: check sizes and stages [08:01] - Getting involved in VC [16:14] - Unicorns in LatAm: Brazil versus Mexico [18:36] - Advice for Spanish-speaking LatAm founders in the Brazilian market [20:52] - Deciding on ONEVC’s investment thesis [23:55] - Advice to Pedro’s younger self [25:10] - Books and podcasts Pedro recommends [29:11] - What’s next for Pedro and ONEVc? Resources Mentioned: ONEVC Rappi Loggi Kovi SendGrid Mailchimp Atlassian Todoist “Start-Up Nation” - Dan Senor “48 Laws of Power” - Robert Greene “Meditations” - Marcus Aurelius “The Score Takes Care of Itself” - Bill Walsh, Craig Walsh, and Steve Jamison “How to Get Rich” - Naval Ravikant
Hannah Christian is the Assistant Director of Career Services at Northwest Missouri State University. Prior to this, Hannah was a research librarian for the university before transitioning into this role. Today, she oversees the library’s social media following and has trained student employees on best social media practices in order for the library to successfully communicate with their younger demographic. Find out more about what Hannah and her team are up to and how they bring awareness to their academic library on this week’s show! Key Takeaways: Who is Hannah and what does she do for Northwest Missouri State University? How does academic library marketing differ from public library marketing? What types of Twitter posts did Hannah find success with? Hannah recruited students that matched with their target demographic so that they could stay up-to-date and trendy on their social media accounts. What types of strategies do Hannah and her team use for Facebook? Quick announcement: Are you struggling with your library’s current website? We have a webinar to help you through this process! How does Hannah make sure that her staff shares things that are on brand and not too off-topic? Hannah would give the students all the credit and she would take the flack from everyone else. It’s important to have your team’s back. What advice does Hannah have for other libraries to help improve their social media engagement? What’s Hannah’s favorite source for staying up-to-date with marketing ideas? Mentioned in This Episode: Meetpiola.com/library-figures MeetPiola.com/webinar NWMissouri.edu Hannah on LinkedIn The Score Takes Care of Itself: My Philosophy of Leadership, by Bill Walsh, Steve Jamison, and Craig Walsh
Dermot Keely, Alan Cawley, Pat Flynn, Craig Walsh, Mikey Drennan and Sam Verdon make up the super six guests selected to help celebrate Between the Stripes LOI podcasts one year anniversary. Kieran & Jon talk in depth on the shambles that is Bray Wanderers as well as updating us on all the latest LOI transfers. There's a look ahead to next weeks European ties, while Kieran attempts to claw back a 5-1 deficit in this weeks St.Mel's Brewery prediction game. Plenty of laughs too along the way to mark this big big night for #BetweenTheStripes so please do listen, rate, subscribe and share on social media. Thank you to all of our listeners for the past 12 months of wonderful support.
This week, Con Murphy and Conan Byrne give the fans a voice as fellow podcasters Karl Reilly and Kieran Burke gush about the League, while Bray Wanderers midfielder Craig Walsh talks about rebuilding his career following his battle with a gambling addiction and serving a doping ban from the game.
Episode 1 - A journey to find the most interesting way to throw projected light at trees. Roly talks about the work of Craig Walsh and his intro to tree projections through a gig at the Fairbridge Folk Festival, leading to the unexpected birth of a mathematical, algorithmic entity called 'Tree Boss'.Spoken and produced by Roly Skender. 'Big Rock' by Stoney Joe.
Episode 1 - A journey to find the most interesting way to throw projected light at trees. Roly talks about the work of Craig Walsh and his intro to tree projections through a gig at the Fairbridge Folk Festival, leading to the unexpected birth of a mathematical, algorithmic entity called 'Tree Boss'.Spoken and produced by Roly Skender. 'Big Rock' by Stoney Joe.
The Student Ministry Podcast | Youth Worker Resources | Leadership Development
In 1979, Bill Walsh became the Head Coach of the San Francisco 49ers. He went on to become one of the greatest coaches in NFL history. In this episode, Kenny talks about some of the great leadership lessons we can learn from Bill Walsh: 1) Develop a successful team-oriented culture 2) Develope a system that maximizes the gifts of your team members 3) Teach people to hate mistakes, but not fear failure Recommended Resources The Score Takes Care of Itself (by Bill Walsh, Steve Jamison, and Craig Walsh)
Multiple Sclerosis Discovery: The Podcast of the MS Discovery Forum
[intro music] Host – Dan Keller Hello, and welcome to Episode Thirty-Seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. This week’s podcast features an interview with Jeanne Loring, who works with human induced pluripotent stem cells in a mouse model of MS. But to begin, we’d like to tell you about one of the most useful features of the MS Discovery Forum. Each week somewhere between 30 and 110 papers related to multiple sclerosis are published in the scientific literature. At MSDF, we endeavor to list them all, publishing links to a curated set of each week’s new papers every Friday at msdiscovery.org/papers. The first step in curating this list is an automated PubMed query that pulls all papers containing the terms multiple sclerosis, myelin, optic neuritis, acute disseminated encephalomyelitis, neuromyelitis optica, transverse myelitis, experimental autoimmune encephalomyelitis, cuprizone, neurodegeneration, microglia, and several related terms. This query returns many false positives. MSDF editors read all the titles and most of the abstracts and make judgments about which papers are directly relevant to MS or related disorders. Last week, for example, the query returned 139 papers and, in our judgment, only 58 of them – 42% – were truly MS-related. Some weeks the proportion is even lower than that. The query terms neurodegeneration, myelin, and microglia are responsible for most of the false positives. Neurodegeneration, in particular, returns many references related to other neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and hypoxia, to name a few. Editorial judgments on which articles are relevant are often subjective, and we frequently struggle with those decisions. It’s easy to decide relevance when an article actually mentions multiple sclerosis. It’s harder when it mentions only myelin or only Th17 cells. If you think we’ve missed an important MS-related article—or if you think we’ve included an irrelevant article—I hope you’ll let us know by emailing us at editor@msdiscovery.org. And we’re open to suggestions on how to adjust our PubMed query to decrease false positives and false negatives. Once we’ve chosen which of the articles to include in the week’s list, we select between two and four of them as Editors’ Picks. Those are the week’s articles that seem to us to be the most important or interesting or intriguing. Once again, we invite readers to take issue with our choices. We’d love to hear about important articles that we have not designated Editors’ Picks or, on the contrary, Editors’ Picks that don’t deserve the honor. [transition music] Now to the interview. Dr. Jeanne Loring is Professor of Developmental Neurobiology and Director of the Center for Regenerative Medicine at the Scripps Research Institute in San Diego. She and her collaborators have been testing human neural precursor cells derived from embryonic stem cells in a mouse model of MS. The cells are injected into the spinal cords of immunocompetent mice with a model of MS induced by a neurotropic hepatitis virus. The cells are rejected within a week, but in that time they suppress the immune system and induce remyelination. Interviewer – Dan Keller In terms of how you came upon your most recent finding about human pluripotent stem cells in the mouse model of MS, could you give me a little bit of the back story? Interviewee – Jeanne Loring Oh yeah, sure. It was really interesting. So Tom Lane and I set out to try to develop a stem cell therapy for MS using human cells. So as a control experiment, we took human pluripotent stem cells, in this case embryonic stem cells, and turned them into neural precursors; differentiated them just a little bit. And then we transplanted them into Tom’s mouse model of MS. These mice were not immunosuppressed, and so we expected the cells to be rejected. And this was just our first experiment. But the results were not what we expected. After the cells were rejected, the mice started getting better, and their clinical scores improved. And then after several months, these mice were almost indistinguishable from normal mice. The first thing we thought was that we’d gotten the cages mixed up, and we were looking at something different. But we’ve repeated the experiment now more than a hundred times, and about 75% of the time we get the same result. So what this tells us is that these cells that we put into the animals are having some effect during the seven days that they exist in the animals that leads to both immunosuppression and remyelination and a clinical improvement which is quite remarkable. MSDF When you say 75% of the time, does that mean you get almost no effect 25 % of the time? Or does it mean that 75% or the mice? Because that would say whether you’re making your stem cells right or not. Dr. Loring It’s 75% of the mice. MSDF How do you explain it at this point, or where do you go from here to find a way to explain it? Dr. Loring So once we’d realized that we had a phenomenon that was repeatable, we realized that there was something special about these cells. And we tested other cell types, like the pluripotent stem cells that they were derived from, and human fibroblasts, and discovered that neither one of those was effective. And since then we’ve also tried other ways of making neural precursor cells, and those cells aren’t effective either. So it’s something extremely special about the cells that we used in these experiments, which is very lucky when you think about it. So we’ve now, both Tom and I – even though we’re not in the same place – we’ve set out to try to find out what it is about these cells that gives them these properties. Our first sort of cut on this – our hypothesis – is that the cells are secreting something that has a lasting effect. Our sort of big picture idea is that there are probably more than one protein or glycoprotein being secreted. And together they suppress the immune system so they act on the inflammatory response so that they increase the number of regulatory T cells that are produced and decrease the other T cell types. And they induce remyelination. So Tom is now working on trying to identify what factors these cells make that are inducing the T regulatory cells. And on my side, we’re trying to identify what it is that makes them remyelinate. MSDF When you make these cells, how do you know you got a good batch? Can you characterize them? Are there biomarkers, and you can say, “We did it right this time?” Dr. Loring Yes. In fact, that turns out to be really important because we did it wrong a few times. And we have a gene expression signature. It’s essentially diagnostic assay for this particular cell type. We’ve boiled it down to a set of qRT-PCR markers. And, because we have collaborators in Australia, we had to be able to transfer this quality control assay to them. So far it seems like those markers, I think it’s a group of 10 or 12 markers, seem to be predictive of the cells’ working in the animals. MSDF And just to clarify, that’s real time quantitative polymerase chain reaction? How are you going about characterizing what they’re doing? I mean, are you doing cytokine measurements or you’re looking at cells that get produced in the mice? Dr. Loring Tom is really handling the cells that get produced in the mouse. He’s doing the T cell analysis. What we’re doing, we developed an in vitro cell culture method to look for the effect of these cells on maturing oligodendroglia in culture. And we found that something secreted by these cells which shows up in their culture medium actually induces maturation of oligos – of OPCs – in vitro. I guess that’s another result that we didn’t expect to be quite so clear. So that shows that there’s something that is secreted by the cells. I mean, that’s the most likely idea. And on Tom’s side, he’s shown that the conditioned medium from the cells induces T-reg generation. And on our side, we’ve shown that conditioned medium from the cells induces oligo maturation. So now we’re trying to figure out what it is in that conditioned medium because now we think we can do a cell-free therapy for MS if we can identify what the factors are. It would be much simpler for us to do even a protein therapy for MS than it is to do a cell therapy. So both sides are taking sort of a candidate gene approach in which we’re identifying the proteins that are most highly specifically expressed in the cells that work in the mice. We have a list of those proteins, and we’ve sort of snatched a few candidates out of that group, and we’re testing to see whether each one of those proteins in purified form has the same effect as the conditioned medium. The other approach, which is more tedious but more likely to actually tell us what’s going on is for us to fractionate the medium into different sized proteins and then test each one of those fractions. We’re in the process of doing that right now. MSDF But it sounds like these cells are pluripotent. Not pluripotent in the normal sense of a stem cell leading to different lineages, but they have a couple of effects. One is the immunomodulatory, the other is regenerating oligodendrocytes. Do you think it really requires the gamish of proteins? If you fractionate them, will you possibly lose the signal? And that’s a big matrix to put back together again. Dr. Loring Yes, it is. And obviously, if we get no signal from our fractions, we’ll put our fractions back together again and try to find out whether – there are only three fractions, really, right now. So we’ll try different combinations of these fractions to try to find out if we can reproduce the effect. The effect is quite robust. We essentially get no maturation in medium conditioned by other cell types, but we get very strong maturation when we use conditioned medium from this particular neural precursor cell. MSDF If you only have three fractions now, is it because you just have chosen not to fractionate it even more until you know what’s going on? Dr. Loring Yes, we’re trying to hone in on it. So we don’t want too many different things to look at right away. I’m hoping that we find that only one of those fractions works, and that we can discover everything is within that fraction, but I really can’t predict what’s going to happen. MSDF It sounds like the approach would be to put everything in except one each time as opposed to keep adding back. You’ve got to find the one critical one missing that makes the thing not work. Dr. Loring Yes, and eventually we will do that with specific antibodies, but right now that is, since we don’t really have our candidates narrowed down enough, that isn’t a viable approach. But you’re absolutely right. We want to find out if that’s missing, whatever the things that are that are missing. And I’m hoping it’s not so complex that it’s five or six or seven proteins, because that’ll make it much harder for us. MSDF How do characterize the condition of the mice? Dr. Loring So that’s Tom’s area of expertise. It’s essentially an observation of the mice over time. We have a movie which I can show you, but I can’t actually do it in a recording. It’s quite obvious when the mice – they’re blind scored so the person who looks at the mice and sees how well they’re walking around doesn’t know whether they’re controls or experimentals. If you just see the movies that are selected at particular times after the cells have been transplanted, it’s quite dramatic. They have a much better clinical score. Essentially, they’re almost normal after six months. MSDF And how are you sure that the cells you injected into the spinal cord are gone, that they’ve been rejected completely? Dr. Loring That’s a good question. We used a method for live imaging of cells in which we use luciferase to label the cells. And then we used an instrument which allows us to image the cells in mice – in living mice – over time. So we did this in individual mice and saw that they disappeared over time. And after eight days we couldn’t detect them anymore. That doesn’t mean there isn’t one or two left because the resolution isn’t that high. We will go back eventually and look through sections of the spinal cords and see whether we can detect any. The other thing we can do is (skip 13:37) a human-specific markers. So we can just take a section of the spinal cord and find out if there’s any human cells in it at all, or any human genes in it at all. But we haven’t done that yet. MSDF Do the cells have to be gone? Have you tried injecting a second time? Dr. Loring No, we haven’t. We don’t know. We really don’t know. It would be very interesting if it reversed the effects. Then we’d really have a problem to solve. MSDF What else is there important to add or that we’ve missed that’s important to this kind of research? Dr. Loring So our dream is that we will identify a group of proteins and the concentration of those proteins necessary to have these two effects in this mouse model. And then we will do some biological engineering. We’ll be putting the cells into these little spheres and matrix that allows slow release of these proteins or controlled release of these proteins. And then, instead of putting cells in, we’ll put these beads in. And I don’t know whether that would end up being the final product or not, but there are lots of ways to deliver proteins, and this one I find rather attractive because it doesn’t require pumps or syringes. And I think that’s certainly the direction we’re going to try to go in. And so Tom Lane and I have just gotten an NIH grant for five years of funding, which seems like a very long time to me. So in five years we will have discovered the best way to deliver these things. We’ll discover what they are and the best way to deliver them. Tom has put conditioned medium into the mice, and it also works. MSDF Because I was going to ask, had you encapsulated the cells just to see that the supernatant does it without cell contact? Dr. Loring It turns out that the conditioned medium itself, you inject that into spinal cord, it’s not as dramatic an effect, but you have a clear clinical improvement. MSDF Have you tried injecting it either IV or intraperitoneally? Dr. Loring Yes. Well, we didn’t inject the conditioned medium. We did try injecting the cells, and they pretty much stayed where we injected them. These cells, unlike mesenchymal stem cells, they aren’t very migratory. So they don’t really have the receptors that cause them to move to areas of inflammation like CXCR4, for example; they don’t express that on their surfaces. So that does not seem to be a good delivery method for these cells. They don’t go anywhere. MSDF I was also thinking that if something they secrete is important, whether it circulates. Maybe they’re not making enough concentration if you inject them outside of the central nervous system, but it seems like you’re going to be faced with a little cumbersome problem in a clinical situation years and years ahead from now if you have to keep injecting proteins into the spinal cord as opposed to more peripheral. Dr. Loring I agree. And the solution to that is generally to look for peripheral effects and then try to suppress those when you do a therapy like this. That’s a long time, and we could certainly imagine how we would do it. But we need to know what those proteins are before we can decide on whether we expect them to have effects peripherally or not. But I agree with you; delivering them intravenously would be far easier. MSDF I know you have a lot of work ahead of you now with this, but is there another animal model of MS – or even another mouse model of MS – where you can see if it works even in a mouse model different from this one? Dr. Loring Yes, we’re actively pursuing that with our collaborators in Australia. And it’s interesting because they’ve gotten some positive preliminary results using the EAE model, but the approach to the EAE model I’ve realized is quite different. Generally, what people do is they provide the therapy at the time that the pathology is developing, and they try to prevent it, which is a really different idea than what we had using the mice that are already paralyzed. So they have found that if you can deliver the cells at least close to the spinal cord, then you can see some effects. The problem is that in Australia, and this is one of those technical things we had not anticipated, they don’t have permission to inject cells into the spinal cord. So they have to go through their animal rights people or their animal protection groups and try to get permission to do so. So with Craig Walsh at UC Irvine we have started doing parallel experiments with the EAE model. I’m not necessarily sure that it’s going to have similar effects. I mean, I really don’t know. MSDF Can you describe how these mice in your experiments were made to have MS? Dr. Loring Yes, they were given a virus, a neurotropic virus, which kills off the oligodendroglia. They become demyelinated, and there is a secondary inflammatory response. So the mice are actually paralyzed in their hind quarters at least by the time we put the cells in. They have to be fed by hand. So this is not a trivial thing to do. But we’re trying to reproduce the effects during the progressive form of MS, for example, or during an attack of MS. So we’re trying to repair the mice or cure the mice that are in a condition which would be similar to the worst case scenario for people with MS. MSDF Do you think this may also have effects not only on the myelin, but also on damaged neurons? Dr. Loring We don’t know, because the mice haven’t really had enough time to get a lot of neuronal damage, but that’s a very good question. We don’t know yet. MSDF I appreciate it. Thank you. Dr. Loring You’re welcome. It was a pleasure. [transition music] Thank you for listening to Episode Thirty-Seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. [outro music]
Listen to the New Years and Mr. Mount Edition of CrowRadio. It includes a new segment of the funny rants of CampusCapers and a few words from BeVP and Mike the Pizza guy in DRAG!!! The Vinnie's DJs are also on CrowRadio 4 giving a shout out to the upcoming semester of fun times.Produced by: Bruno Perron & Mike McGuireSpecial Guests: Matt MacAulay, Morris MacLeod, Craig Walsh & Megan PowerMusic by: HermitWritten by: Bruno PerronVocals by: BeVP, Hermit & MC Silence
National Gallery of Australia | Audio Tour | The National Sculpture Prize and Exhibition 2005
Cross-reference continues a series of interventionist works that address the public, private and transitional aspects of both the gallery space and other public spaces. The defined architectural boundaries of the gallery site are ruptured through an open door, which not only expose an external environment but also provides alternative access to the internal exhibition. As participants of the Big Day Out music festival appear to examine the gallery, its art and its audience, the gallery public also experience an unexpected view of the music festival and its audience. The work not only inverts the space of the exhibition but the uncertainty created between the artwork/viewer is literally mirrored between the exhibition/external public space. The juxtaposition of two disparate sites and the simulated interaction between the participants of these sites aims to disrupt preconceived expectations of specific cultural and social contexts, and the way in which audiences are conditioned to interact and participate. The work consisted not only of the projection located in and beyond the gallery wall but as a temporal public sculpture within the Big Day Out site. A scale model of the gallery, inclusive of miniature art and audience, was positioned within the festival; the festival audience viewed the contents through a miniature doorway while their interactions were recorded through a camera mounted within. The location of this sculpture and its unexpected presence within a music festival context fulfils a similar objective to gallery-based work: that is, to disrupt the formal and participatory conventions associated with specific cultural and social experiences. Image: Installation view at Adelaide Biennale of Australian Art, AGSA Photography: Mark Bradley