The Climate Biotech Podcast

Meet the founders, Part 1: Homeworld Collective's Founding Scientist, Paul Reginato

• Homeworld Collective • Season 1 • Episode 5

Share episode

How does a love for life and a deep passion for science fuel groundbreaking climate solutions? Join us as we spotlight Homeworld Founding Scientist Paul Reginato, who launched Homeworld Collective alongside Dan Goodwin to empower the climate biotech community.

Paul shares his journey, from starting as an aspiring young artist, to falling in love with biology as an undergraduate, to developing foundational in situ sequencing tech as a PhD researcher at MIT, to leading community roadmapping efforts for open problems in climate biotech. 

We explore how microbes can help in mitigating greenhouse gas emissions and how communicating open problems can empower innovation in a community.


(00:00) Introduction to the Climate Biotech Podcast
(00:43) Meet the Hosts: Dan Goodwin and Paul Reginato
(01:38) Paul Reginato's Journey: From Art to Biology
(02:45) The Intersection of Love and Science
(03:27) Founding Homeworld Collective
(07:32) The Grind of Scientific Research
(10:19) From PhD to Climate Biotech
(13:41) The Problem Statement Repository
(21:20) Connecting Funders with Science
(22:07) Exploring Climate Biotech Problems
(22:47) Biology and Mineral Interactions
(23:56) Innovations in Mining and Carbon Management
(26:54) Microbial Community Functions in Mineral Weathering
(28:25) Challenges in Carbon Capture
(30:40) Community-Centric Approach at Homeworld
(35:10) Rapid Fire Questions with Paul
(39:23) Advice for Aspiring Biologists
(40:49) Dreams for Homeworld Collective
(42:10) Conclusion and Contact Information

Send us a text

Dan Goodwin:

Welcome to the Climate Biotech podcast, where we explore the most important problems at the intersection of climate and biology and, most importantly, how we can solve them. I'm Dan Goodwin, a technologist who spent years transitioning from software and neuroscience to a career in climate biotechnology. As your host, I will interview our sector's most creative voices, from scientists and entrepreneurs to policymakers and investors. Welcome everybody to this episode of the Climate Biotech Podcast. We've learned over 45-ish or so interviews with subject matter experts and leading practitioners. It's fun to ask people who they are, what they do and help create a narrative arc of what made this person do what they do. It's also really important to just turn that lens in on ourself and have a fun conversation.

Dan Goodwin:

So here this is going to be me, daniel Goodwin, co-founder and executive director of Homeworld Collective, and my co-founder and founding scientist of Homeworld Collective, paul Reginato. This is a really fun story for us because we go back to 2015. And a fun little trivia to set this up is that Paul was the first person to show me how to use a pipette when we met in our PhD programs at MIT in September of 2015. So this is a fun conversation for us to take a step back and talk about why we made Homeworld, and also to help introduce the world to who we are. Hopefully, that helps everyone engage and get excited about the field of climate biotech. So, paul Reginato, my friend since 2015,. Who are you?

Paul Reginato:

and where did you grow up? So I grew up in Canada, in Kitchener, ontario, which is close to Waterloo, which is close to Toronto, and as a young person I loved art and science, particularly music and physics. I started college studying contemporary music at Humber College in Toronto, wanting to pursue songwriting. I still make art now, mostly poetry and photography. But I realized that that wasn't the life I wanted to lead, even though I loved everything that I was doing. And so I switched into physics at University of Waterloo and you know, I was fascinated by the foundational underpinnings of nature. And then one day I went to this lecture on molecular biology and the next day I impulsively changed my major to biology, molecular biology. And the next day I impulsively changed my major to biology because I was just so blown away by, like, what was happening in that field.

Paul Reginato:

And as I went on I sort of fell in love with biology and with life itself, which I think is such a beautiful mystery.

Paul Reginato:

And you know, as time went on, that fascination with life sort of became something you could maybe call spiritual for me. The way I see it, if anything is sacred it's life, and as a part of life we have the opportunity to shape what life is by shaping ourselves and the world around us. The most amazing thing to me is that we have the ability for loving action and by cultivating that, we can actually create a world with more love in it, because we are those agents of life, along with everybody else and everything else. All of that led me to the North Star, which is to do my best to frame the big parts of my own life in terms of love for life itself, which includes me and people close to me, but also all life on Earth. I always try to frame my attitude that way to make decisions. That is what led me into climate tech and merging the technology of life and biotech with sustainability.

Dan Goodwin:

So when you were shifting your major into biology, did you know you'd one day be founding a nonprofit to build the field of climate biotech?

Paul Reginato:

Definitely not. I always figured I'd be doing some kind of science, philosophy or art. Probably not technology. That's probably like at the bottom of my list. My dad's an engineer and people would always ask me if I wanted to become an engineer, and I always say probably not. Technology, that's probably like at the bottom of my list. My dad's an engineer and people would always ask me if I wanted to become an engineer and I always say probably not. But you know, one thing led to the next.

Paul Reginato:

And through my life I've had many ideas of what I want to do. Those have been based on my passions and interests at the time. For a while I wanted to do some form of biology. I was interested in sort of like, the foundational underpinnings of like what is life, and then I started to get interested in measurement technologies for biology to help us advance our understanding of life. I see my life's work as a series of projects. I stopped committing my entire life to something because I always see that it just changes, and so I you know I got into biotech because I wanted to. I wanted to, like I said, develop measurement tech that would help us do biology better. When I went to study biological engineering at MIT, you know what attracted me to Ed Boyden and George Church's labs. They're very focused on technology. A lot of the technology was to enable better science and better biology. So I still identified as a scientist at heart during that time.

Paul Reginato:

In the last few years of my PhD, I came to this crossroad, stepping back and this framing for me this relationship with life and trying to love for life. I was picking between two forms of love to understand or to care for life. I was thinking about. You know, maybe I'm going to go and try to get deeper into the foundations of theoretical biology. I was interested in the Santa Fe Institute and all this complex system stuff. And then on the other side, it was like what can we do to protect life on this planet? Because humanity and the planet is in a crisis right now because human activities have led to ecosystem destruction we talked about the sixth mass extinction, climate change. These are huge problems. I wound up choosing technology and going on the most applied route because it's like how can I use my skills and understanding to care for life on this planet?

Paul Reginato:

You and I, dan, going through that together, right, we had this similar personal reckoning and we're exploring what biotech could do for climate tech and as we were figuring out those ideas, we had some opportunities to pursue them. At MIT. There's the MIT Climate Grand Challenge, this funding opportunity that gave people the opportunity to propose new projects that their discipline could contribute to climate tech and that was really catalytic for us because it gave us license to dig into a project and some ideas. We were thinking about biotech and enhanced weathering and geochemical carbon management. At that time, after my PhD, after taking a break and working on art for six months I came back and I got a grant from Additional Ventures to do some roadmapping in biotech for carbon removal. Then, through all this time, dan and I got a grant from Additional Ventures to do some road mapping in biotech for carbon removal.

Paul Reginato:

Then through all this time, dan and I were kind of always talking about some of this more meta stuff about the field of climate, biotech in the community and how the community needed enablement, and we can talk a little more about that later. But it was really that community perspective that we gained from meeting people and exploring in the space that led us to recognize the needs that would one day become Homeworld. And that was just a very organic process that evolved from where I was at the time, the perspectives I had and what I understood to be an opportunity that aligned with my passions and what the world needed an opportunity that aligned with my passions and what the world needed.

Dan Goodwin:

So one thing that's fun to hover on as we can leave talking about your past and move to talk about your present and future is that I think a lot of people today, especially in climate biotech, will discover Paul Reginato as Paul the roadmapper, paul the lead author of an 80 page deep dive in carbonic anhydrase for carbon capture, paul doing fantastic, really inventing how we do scalable roadmapping in science. But one thing that people might not know is that the Paul Reginato I met in 2015 was the vicious grinder at the bench. When I first met Paul Reginato, he had two bench labs filled with all these variants of hydrogels and they smelled terrible. And so I think this is a big part of your credibility as a scientist is that when you do roadmapping, you've got the credibility that you can do the really nitty gritty like science, grind it out, do the 10,000 variants by hand if needed, but then also zoom back. It was 2014, I think. You started your bioengineering PhD with George Church and at Boyden, and then you finished in 2022, was it One 2021.?

Paul Reginato:

2021,. Wow, when I went into my PhD, I didn't know what I was getting into. A good friend of mine, jacob, likened a PhD to entering a fancy castle. You walk up to the castle and it's like come into the castle and you're all enamored by how beautiful it is and then, as you walk in, the door slams behind you and it's like all right, now escape. And then you have to figure out what you're going to do to get out of this castle and that's sort of like a little dramatic, but that's how it can feel as you're going through it.

Paul Reginato:

We both were pursuing these new measurement technologies. We were both working on in-situ sequencing, which is like spatially resolved sequencing of nucleic acids, combining that with expansion microscopy, and this was like foundational tech to Dev and it was gritty. As we got into the weeds. I was just trying to do the experiments to make it work. There were long protocols, some like 10, 12 hour protocols. If I wanted to fit them all into one day. I just did what I had to do and I loved it.

Paul Reginato:

I love attention to detail. I do love thinking about all the details of something, understanding them and finding where the problems are and where the questions are, and I take that into the roadmapping that I do now. It's like what is the possibility for what a technology could be that we're trying to build? And then what are the limiting factors? How can we understand those limiting factors better? How can we find solutions to them? And I think my PhD work was one example of a technology and one example of trying to find those limiting factors. And that mindset is what I bring into our technology work. This mindset I learned from Ed Boyden. He explicitly would always be driving into us like think backward from the problem. Think about a goal and what are the possible ways to get there In that possibility space. Break that down into limiting factors. What's preventing you from realizing that possibility? That addresses the big problem. Try to find multiple pathways that look like they could be solved and then do that research.

Dan Goodwin:

I think that's great, and as we transition into looking more forward, I do want to be rooted in the work that you did in your PhD. You have this line, which I use a lot and I think it's so smart and I always give you attribution for it when we did the work in our PhDs, we worked on things that were too small to see, but then, when we work on climate, we deal with things that are too big to see. I'm really curious, as we start focusing this conversation on problems, I think the audience would be interested in the problems you were solving in your PhD and the problems you were solving now.

Paul Reginato:

In my PhD it was about foundational biology, enabling us to understand epigenetics and how the genome works. As a physical object. We're used to thinking of DNA as a string, almost like a computer code, but in reality it's like in human cells. It's this two meter long, two nanometer thick thread that is wound up inside the nucleus of a cell. That's like 20 microns across, which is about a fifth of a human hair or even smaller, and it turns out that spatial existence of this molecule is an enormous part of how it functions. I sort of think of DNA as this thread that moves around and contacts itself in different places to regulate the information in it, and there's all these proteins and RNAs that are involved in that organization and it's really hard to measure that. We were developing in-situ sequencing technologies to resolve the spatial locations of DNA sequences with high resolution in intact fixed cells and tissues so that we could see how the genome is actually configured and what are the co-localizations of different structures and molecules with different parts of the genome to understand epigenetic regulation. That's why we're using expansion microscopy, which is like super resolution.

Paul Reginato:

One of the most interesting problems in climate biotech is how we can influence biology in natural ecosystems and landscapes, looking at an ecosystem that is gigantic. And you know we have problems like runaway emissions of nitrous oxide or methane from permafrost or agriculture, wetlands or sinks of methane into forests. Those are the main gigascale fluxes happening on Earth, especially for the non-CO2 gases, methane and nitrous oxide. If we want to shift those microbial populations, the cycles of these gases, we're going to have to come up with ways to work with their biology, rather than trying to do some sort of targeted edit. That's really constrained. It's more like nudging things in the right direction using the right kind of finesse, but I don't really know how that works.

Paul Reginato:

That's a very biological problem. There's no solution to that problem. And then the other one is invasive species. What are you going to do about invasive species? We have all these invasive fungi and insects that are destroying plant populations, and invasive vines and invasive predators. This is a biological problem that to solve it requires engaging with biology, but these are really outstanding issues. If we can't solve these problems, we're in hot water. Yeah.

Dan Goodwin:

So one thing that I think people will not realize is that when we at Homeworld say the word problem, oftentimes it's with a capital P. We've become really specific with what a problem is and why it's important. When we worked in neuroscience, we worked on things that are too small to see. When we work on climate, we're dealing with things that are too big to see. It's really hard to just pick a theme and say, okay, we're going to solve greenhouse gas removal or the theme of runaway emissions. I think it's really hard for people to jump in and be effective. So at Homeworld we talk about a problem with a capital P. I think it'd be great for you to explain how you came to this formulation and how we see that coming into the problem statement repository.

Paul Reginato:

So so every day when you go to work, you're solving some kind of problem, right? If you're a researcher or a technical developer, that problem is your problem. It's what you're going to try to solve, which will then contribute to a bigger problem. So if you're working in greenhouse gas removal, your job when you go to work isn't to pull a gigaton of carbon out of the sky. That might be your goal eventually, but your problem that day or with that project might be to understand the way a biological mechanism interfaces with a mineral to generate alkalinity, which can then, through many downstream integrations with other parts of a technology, result in carbon drawdown and then be scaled up to gigaton scale. And so, when people are looking to address these big problems that we have in climate change, they need problems that they can go to work and solve, that they can actually personally work on Recognizing that. As an organization that wants to enable practitioners, we've started to develop a focus on what we call problem statements. The problem statements are a way you can check them out. If you go to our problem statement repository, you can see a collection of problem statements that are concise one page to one and a half page descriptions of problems that should be addressable by one person or up to a lab-sized team that fit into a frontier challenge in climate tech.

Paul Reginato:

The way we generate those is by talking to our community and learning, helping the community articulate problems that they wish other people knew more about so that the community could bring its ingenuity to solve them. And there's this kind of motto that I bring to that, which is the way to know everything, is to have friends who know everything. If you have a problem that requires diverse knowledge, articulate that problem to the community and tell them why it's important and what needs to happen to make progress toward the big, important goal. And so we collaborate with community members to articulate these problems, then share them in the problem statement repository. Our big challenge with the problem statement repository is to figure out how to make it easy and aligned with people's incentives to share problems with their broader community so that we can have a culture of knowledge and problem sharing that lifts everybody's boats and helps us all move toward the collective action problems that we're trying to solve. I think it's great and I think it really is a big culture change that we're trying to solve.

Dan Goodwin:

I think it's great and I think it really is a big culture change that we're trying to enact here to build more of a problem centricity in these big fields. I think what you said is a really good point. We do the work because we believe deeply that if somebody writes a problem statement to the world, it's in that person's interest and that person benefits. Would you have some examples or some thoughts about how an author of a problem statement in the public would benefit from it and how the field also benefits from it?

Paul Reginato:

I think a great example is if somebody has a problem they recognize as important but it might not be in their wheelhouse or on their personal agenda to solve. An example would be we've had great conversations with a researcher named Sonia Salmon at North Carolina State University who is developing technology to use the enzyme carbonic anhydrase as a catalyst for CO2 exchange in carbon management technologies like carbon capture technologies from point source CO2 emissions or direct air capture, and Sonia is an expert in the carbon management technologies themselves and the role that a catalyst can play and how a catalyst can be incorporated into materials that can be implemented in these carbon management technologies. But Sonia is not a protein engineer and so in her lab she's not modifying the carbonic anhydrase enzyme to make it fit best and perform best for a carbon capture application. And so we talked to Sonia about what are some problems you wish protein engineers would know about. But if they do have the ability to modify the carbonic anhydrase enzyme, what would you want them to do so that carbonic anhydrase can best be used for the applications you're developing? This is a great case where Sonia is incentivized to share this because solving this problem is outside of her personal work. No one's going to be scooping her. If someone else were to solve this, it would help move towards solutions to the problem she's trying to solve and be good for the world, because these problems are about a sustainable way of living. She shared a problem with us.

Paul Reginato:

It was a very simple goal. It was lower the Km of carbonic anhydrase. The Km is a property of an enzyme that describes how strongly it interacts with its substrate. Carbonic anhydrase actually has a pretty high Km, which means that it interacts strongly with CO2 when CO2 is at a high concentration. But when CO2 is at a really low concentration, like it is in direct air capture, carbonic anhydrase doesn't catalyze CO2 exchange as effectively because it just doesn't interact with CO2 strongly enough. But it is still an effective enzyme at those concentrations. But if you could lower the Km you could make the enzyme work better. That's the reason I love that problem, because it's such a well-proposed problem.

Paul Reginato:

You don't need to know anything about carbon management to approach reducing the Km of carbonic anhydrase. All you need to understand is protein science and the assay that you would develop to measure it. I think that's a great example and other reasons why someone might be incentivized to participate by communicating an idea, especially if it's one that you're not currently trying to solve, you get some credit for that idea. When people encounter that idea, they associate your name with it. If they want to learn more about it, they might reach out to you, but it helps you connect with people who are interested in solving a problem you're working on from a complementary standpoint. 100%.

Dan Goodwin:

And just to build on that too. There's also the other side of people trying to do something impactful for climate believe that synthetic biology, or just biology in general, is an important platform, but I have no idea where to start looking. So developing a problem statement repository that is trusted in rigor but open to anybody who wants to contribute is a great way for these people to discover or find funders that might want to support the work.

Paul Reginato:

I think there's a lot of people looking to support science. We hope that supporters of science, people who want to fund science, people who want to design research programs will take a look at these problem statements to get some inspiration. I mean, the problem statements are short. They're not going to tell you everything there is to know about this problem. They're basically just telling you what the core problem is you're trying to solve and why it's important conceptually. If you want to learn more, you can look at the references in the problem statement or reach out to us or one of the contributors to the problem statement.

Dan Goodwin:

Yeah, I really love this and so we can talk about other people and their problems and other people looking to support problems, but it's also fun just to ask you directly what are your problems that you're really interested in?

Paul Reginato:

climate, biotech influence biology at the scale of landscapes or ecosystems, I think is something that we really need to figure out. That isn't something I'm actually personally working on really yet, but that I think is a really important problem and that's somewhere that I would like to take my work with Homeworld in the future. Currently, we've been thinking a lot about the intersection between biology and minerals. There's this amazing fact that I learned recently, which is that the mineralogy of Earth is more diverse than the mineralogy of any other planet in our solar system. My understanding is that the reason for that is because of life, because life transforms minerals. Organisms will dissolve minerals to extract nutrients or precipitate minerals to make structures in their biology or even cause mineral precipitation as the result of catalyzing other reactions. And you know we're all used to thinking about, you know, photosynthesis as this process of life where light and water and carbon come together to produce life. But really it's also rocks. It's air, water, light and rocks that come together to make life.

Paul Reginato:

And geobiology has historically mostly been a pure science, hasn't really been applied to technology for the most part, with some very important, notable exceptions in biomining and bioremediation. Now we're encountering an age of technology where we really need a lot of innovation in mining and carbon management. The reason we need innovation in mining is just so that we can sustainably harvest the metals that we need for the energy transition. And there's all these mechanisms, biological mechanisms that are understudied or, many of them, unknown, that perform the mineral transformations we need for mining or that we need for geochemical carbon management. And understanding how those mechanisms work, understanding how to work with them efficiently so that we can develop technologies, and understanding also what the real needs are of those industries, like what are the needs in mining that some of these biological processes could solve, and how can we create a bridge between geobiology, biotechnology and mining that connects practical problems in mining to open problems in geobiology, to build new technology. For that Got it.

Dan Goodwin:

I love this. I think it's great to use the Sonia Salmon example of boiling down a carbon capture problem to a KM formulation for approach engineers, and if that's the endpoint of a well-framed problem, it's fun to think about the two big themes that you just mentioned for the interface of geology and biology. One of them is the metals transition and metals mining. The other one is carbon management, and while metals might be immediately obvious, before we go into finding the eventual problems to boil it down to, it's worth telling the audience what the high-level thing is. What do you mean? Carbon capture in rocks?

Paul Reginato:

Oh yeah, Thanks for asking for that, Dan. When rocks dissolve or when minerals dissolve, they will create either an acidic or alkaline chemistry. In acidic or alkaline chemistry For the ones that produce an alkaline chemistry, alkalinity can react with CO2, which actually is an acid. When it dissolves in water, it produces carbonic acid. That alkalinity from the minerals can consume CO2, and then that CO2 will be stored in solution, either as bicarbonate or carbonate ions, or it'll react with the alkalinity and form a new mineral as a solid carbonate like a calcium carbonate or magnesium carbonate. That underpins a whole family of proposed technologies for carbon dioxide removal from the atmosphere and a carbon dioxide storage in the subsurface. Collectively, we call that carbon management storage in the subsurface.

Dan Goodwin:

Collectively we call that carbon management. This is one of the most scalable ways of the things that give us hope for scalable carbon capture. Creating carbonates is hopefully one of the most durable on a large scale in theory. What would you say are some example problems that we're discovering there that might be addressable by the larger community?

Paul Reginato:

I was just trying to decide which one to choose, addressable by the larger community.

Paul Reginato:

I was just trying to decide which one to choose.

Paul Reginato:

I'll go for a fundamental science problem.

Paul Reginato:

It's still an open question largely what the microbial community functions are that lead to mineral weathering in soils or in more rocky environments. When I say a microbial community function I mean like what are the metabolic pathways and the overall processes in the microbial community that translate the environmental gradients into mechanisms that weather rocks or dissolve rocks to release alkalinity? And so there's a lot of metagenomic, transcriptomic study, metabolomic study to be done on those microbial communities, and then also study on looking at the surfaces of those minerals or the chemistry around them and relating that to the microbial community function to get at mechanisms. That's really important because it shows us what the natural mechanisms are that we can leverage for accelerating the generation of alkalinity. What are the environmental conditions that give rise to certain functions, so that we can then try to modulate those conditions that would encourage microbial communities to move in a functional direction that would cause weathering, and there's something really interesting here with respect to carbon capture in rocks, there's one thing that you and I learned all the way back in 2021.

Dan Goodwin:

I think we first started looking at this, which is that at first it seems like it's really simple and you just want to kick off the calciums and magnesiums to create carbonates, but then we learned that there's a much more complex thing going on, with or without the biology, and that's the passivation layer that stops the reaction of these ground-up rocks to form the carbonates we need for carbon capture. And so it kind of feels like a flashback to some of the PhD work you were describing, where DNA is not just a one-dimensional thing that we read on a screen. It's a three-dimensional object that bumps into itself in space. The rocks that we're trying to weather to capture carbon have multiple processes. Some are speeding it up and some are inhibiting these carbon capture processes. As you've dug through this, do you feel that there's actionable problems or actionable problem potential in these interacting efforts?

Paul Reginato:

Yeah, I love this question. It's so in the weeds. In the weeds is where the real relevant details live. When minerals dissolve, it's a chemical process and there's various factors that can contribute to the formation of a layer on top of a dissolving mineral that will prevent that mineral from further dissolving and hopefully generating alkalinity. Different metals can dissolve at different rates from the mineral framework because they have different energies and different activation energies for getting kicked out of that mineral framework. So an example is if you have a mineral that contains sodium, magnesium, calcium and silica, which is often like this kind of polymerized framework in which the different metal ions come out at different rates, then you'll be left with this sort of shell of silica with some alkalinity leached out of it but other metal ions still sitting in it. It's too. It's too in the weeds, to describe it succinctly. I would have wanted to prepare for it, but I appreciate where you're pushing it.

Dan Goodwin:

Yeah Well, happy to. So we're going to zoom back. We're going to go more meta. The work we do at Homeworld is really community centric. We meet with awesome practitioners doing cutting edge work on deploying biotech to climate goals and planetary health. Oftentimes, I'm sure in these conversations, you're asking questions that feel repeated. Can you share questions that you find yourself asking again and again to practitioners?

Paul Reginato:

I think the biggest, most common question that I usually ask is what is the limiting progress on the bigger challenge that you're trying to solve? Every day we go to work, we work on small problems, but those are contributing to big challenges, right? So usually I'll try to take a step back, like what is limiting progress on the big challenge that the ideas we're talking about are trying to solve, and how does the current idea that we're talking about address those problems? Are we sure that it's the right pathway? And if we do think that it's a really viable pathway, like, what are the most important things we can do to either figure out whether this is a good pathway which would be like if we're not sure yet whether, for example, atmospheric methane removal via a bioreactor system is economically viable, because we don't fully have the design and the techno-economic analysis all mapped out what can we do to understand better the ultimate possibility for this pathway and, in terms of technology, what can we do to solve the most immediate limiting factors and who do we need to enroll to do that? What are the skill sets that are needed for this and the like disciplinary points of view that are needed, because I think we're all used to asking ourselves how our immediate skills can solve some problem. That sort of looks like it could contribute to a big problem, but we're not as trained to ask what other skill sets and what other points of view might be better solutions or might be complementary, because those are not necessarily the resources that we have.

Paul Reginato:

And I think at Homeworld we're really lucky to get to ask those questions and then, in response to those answers, we can try to connect people with diverse skill sets to figure out the problem.

Dan Goodwin:

It's fun to discuss this because I think it can be helpful for people listening. What you're saying might sound obvious. Right From a zero knowledge perspective you might say yes, of course you want to solve a problem that's leading towards a frontier goal and tackling a major benchmark. That sounds obvious, but that's not the baseline we see in a lot of standard academics and I think this is this culture change of trying to create more problem centricity in the field. Let me know if you feel otherwise, but the default I see is oftentimes people are vaguely searching around a field that that lab has worked in before. So it's much more the proverbial running around with a hammer looking for a nail and people are talking less about hey, wouldn't it be amazing if we could solve this frontier goal and this is that little part of it that we're trying to cut off? Does that sound about right from what you see?

Paul Reginato:

I think so. Yeah, I do, and I think enabling people to match their talents and abilities with the right problems is one of the biggest things that we want to do at Homeworld, Because when people have that alignment, it's easier to feel that motivation to do your work, when you feel like you have a clear avenue and see that line between you and impact. Enabling this to be a community effort where people feel comfortable and empowered to recruit the expertise and ingenuity of others is like that's what I want Homeworld to do. That is really my biggest dream for Homeworld that it would be that kind of catalyst that would enable people to solve the problems that are most meaningful to them.

Dan Goodwin:

A hundred percent. There's an implicit empathy to what you're saying here. There's fear with a lot of science now, which is there's risk. Every time you go on a new project that's different from your core lab's work, there's insecurity. Part of what you're saying is that when we help the community find projects and find ways to resource those projects, this is helping people actually do that shift into this cultural shift, into problem centricity. Now, paul, with the last few minutes that we have, we're going to play the game of a few rapid fire questions. First of all, are you ready? I'm ready. Can you remember one article or idea that changed the way you think about biology?

Paul Reginato:

Yeah, there are a few things I've learned in life that really changed my view of nature. One of them is, like we probably have all had that moment when we learned about relativity or quantum physics or like really that's what nature is like and you know early on, like I think we've all experienced, like when you learn about DNA and the fact that there's this fairly simple code that winds up producing a lot of complex stuff. That's really sort of life-changing Then later in life. So during my PhD, I learned about this mechanism of phase separation in biology, where biomolecules, proteins or RNAs will condense into droplets inside cells through a mechanism that's kind of like, you know, like aqueous versus hydrophobic phase that we're used to thinking about in chemistry. But because these biomolecules like are so complex and have so many different ways of interacting, it's almost like there are like many different possible phases ways of interacting. It's almost like there are like many different possible phases. So instead of just two, it's like this high dimensional space of possible different phases and you get these like droplets that form so they're like membrane.

Paul Reginato:

Less organelles turns out is like this and people have hypothesized there are these organelles at at the junctions of neurons, synthesize these organelles. At the junctions of neurons there's stress granules that have this characteristic and a whole bunch of other ones. They can partition different other biomolecules into those separate phases. Just different molecules will have solubility in water or in a hydrophobic phase. This turned out to be a pretty important organizing principle for biology and that's why you get like just to riff on it a little longer. Like you know, there are these proteins we're used to thinking about, proteins that have structures, and there's these proteins that have these disordered domains which don't really fold into a specific structure, and it turns out that in many cases these disorder domains are like sort of generating a phase-like characteristic that, at the right concentration, can cause condensation into a droplet that will create this mini chemical world within a world that will organize other molecules.

Dan Goodwin:

All right so what did this call begin?

Paul Reginato:

Liquid separation, good phase separation or biomolecular condensates. Right, okay, so that.

Dan Goodwin:

I'm going to say that's going to answer one of the questions, which is what's your favorite factoid from nature, I think, the fact that these exist at all.

Paul Reginato:

I think, kind of checks out that question. Can I share a different factoid, of course? So I learned about this exoplanet called WASP-121b and it's this like Jupiter-like planet that's really close to its star. It is phase locked with the star, meaning that like as it orbits, the same side of the planet is always facing the star. So there's this really hot side of the planet and a really cold side, and on the hot side minerals will like gasify, so you'll have like a lot of gaseous rocks because it's just so hot, and then, like that, will convectively flow over to the cold side where it condenses and then you get like rain of like metals and like minerals, like you'll get like raining rubies and sapphires, they think, on this planet.

Paul Reginato:

And I just love imagining these other worlds out there that are so different than what we have here but have these like amazing details that I guess presumably there's no life on wasp 12121b. It's like a pretty intense place. If that's true, that means there's no one there like observing these details. But I think it's really cool that, like from Earth, we can appreciate the beauty of this exoplanet. That's like light years away.

Dan Goodwin:

And what's one bit of advice for junior people getting into biology?

Paul Reginato:

for junior people getting into biology.

Paul Reginato:

For junior people getting into biology, I would say don't be afraid of so-called weird organisms. You know the history of biology was really built on studying a small number of organisms and that, you know, brought the convenience of learning how to work with them. You know, humanity sort of cutting our teeth on this difficult discipline of biology, but a lot of the problems we have to solve now involve organisms that are not E coli, are not Drosophila or fruit flies, are not frogs, are not mice and are not humans. They're and are not Arabidopsis right, they're different kinds of plants, fungus, extremophiles, microbial ecologies. And understanding the secrets and powers and mechanisms and ways of life of those organisms, I think is a big part of the future of biology and is a big part of solving the challenges that we have in climate biotech and in climate sustainability. And you will not be the only one venturing into these strange waters. These are where a lot of the important frontiers are and there's going to be other smart people going there with you and you'll figure it out Awesome.

Dan Goodwin:

One more question, and then we want to wrap up with where people can find you, which is, what is one dream you have for Homeworld Collective next year?

Paul Reginato:

for someone who will lead that program and I really hope that we can, through our geobiotechnology program, get better at really understanding the needs of industry and mapping those problems that researchers can solve, because I think in something like mining it's such a gigantic industry with so many established practices and so much heterogeneity and the kinds of problems that it encounters on sites, and you're not going to be able to impact an industry like mining by having like academic ideas only and by having like lab scale ideas only. You really have to understand the needs of that industry and that's, I think, really important for a lot of the areas that Homeworld would work in. I want to see us mature in that direction next year because I think that's really one of the most important things that we can do to enable innovation.

Dan Goodwin:

All right, so Paul Reginato, my good friend since 2015.

Paul Reginato:

As we wrap this up, how can people find you and what would you point them to? Yeah, so I would say, check out our website homeworldbio. Look at the problem statement repository so far has been the part of our work that I've worked on the most and, yeah, I hope that helps you learn about problems and connect to opportunities that we can help with. And if you want to reach out, you can check out hello at homeworldbio and drop us a line.

Dan Goodwin:

Thank you so much for tuning into this episode of the Climate Biotech Podcast. We hope this has been educational, inspirational and fun for you as you navigate your own journey and bring the best of biotech into planetary scale solutions. We'll be back with another one soon and in the meantime, stay in touch with Homeworld Collective on LinkedIn, twitter or Blue Sky. Links are all in the show notes. Huge thanks for our producer, dave Clark, associate producer Arya Natarajan and operations lead, paul Himmelstein, for making these episodes happen. Catch you on the next one.