Plant Synthetic Biology for Methane Mitigation with Eli Hornstein

On this episode of The Climate Biotech Podcast, Paul is joined by Eli Hornstein, founder and CEO of Elysia Bio, a company engineering feed crops to address methane emissions from livestock. Eli came to plant biotech through an unlikely path: undergraduate degrees in ecology and linguistics, conservation fieldwork across East Africa and South America, and a Fulbright Fellowship in Mongolia before a PhD in plant genetic engineering at NC State. That ecological background shapes how Eli thinks about intervention points in agriculture.

One of Eli’s core insights is that plant biotech has spent decades optimizing plants for the plant's sake while largely ignoring that those plants are actually for feeding animals. Enteric methane from ruminants is the single largest source of methane on Earth – larger than oil and gas – and most of those animals are on pasture with few practical options for emissions reduction. 

Elysia's first trait encodes bromoform, a methane-inhibiting compound from red seaweed, directly into corn so farmers don't need to change feeding practices. The company has since expanded into pasture grasses and other crops to reach ruminants outside commodity feed systems. Their most ambitious project, the PlaMMO Project, engineers plants to express methane monooxygenase (MMO), the enzyme methanotrophs use to oxidize methane, potentially enabling crops to pull methane directly from the atmosphere. Elysia is currently running analytical chemistry on their first MMO-expressing plant candidates.

Listen to learn about the community of researchers working to de-risk heterologous MMO expression, why plant synthetic biology is underrated relative to microbial systems, and why Eli thinks ecological thinking is one of the most undervalued skills in biotech. Plus, learn how a photosynthesizing sea slug inspired a company name.

Transcript

Cold Open On Engineering Feed Crops

SPEAKER_00 0:04

We kind of work on multiple fronts within that big idea of feed crops that are engineered to solve livestock problems. And I'll try to explain where the multiple fronts come from. So the very first place we started was can we engineer feed crops to get rid of enteric methane?

Meet Eli Hornstein

SPEAKER_01 0:26

Welcome to the Climate Biotech podcast, where we explore the most important problems in climate and environmental biotechnology and how we can solve them. I'm Paul Reginado, co-founder and executive director of Homeworld Collective. Together, we have agency to build technologies that enable a brighter future for all life on earth. Before we get started, a quick note for listeners planning to attend SinBio Beta this year. You can use the discount code HomeWorld2026 in all caps, no spaces, to get a 10% discount on any ticket. Big thanks to Aaron Blotnik for making this discount possible. And while you're at the conference, please swing by the Biomining panel on May 5th, hosted by Homeworld's Critical Minerals program lead, Jamie Falbuska, titled DNA over dynamite: how biomining is transforming resource recovery. I am here with Eli Hornstein, who is the CEO of Ilycia Bio, and in my experience is a man of interesting projects. And so I'm very excited to talk to Eli about his work with plant engineering and his journey into building some very interesting climate technologies using plants.

SPEAKER_00 1:38

Nice to see you.

From Conservation To Plant Biotech

SPEAKER_01 1:39

Thank you so much for joining us, Eli. So let's just start with a bit of background about you. Where did you grow up and how did you get here? Did you always know that you'd be a plant biotechnologist?

SPEAKER_00 1:51

Okay, so I'm coming to you from Raleigh, North Carolina, which is the same town I was born in. However, when I was five, we moved to Eritrea. This was in the 90s. And Eritrea, it is it's a country right next to Ethiopia, which at that time had just come into existence. And so as far as the question of where did I grow up, you know, we were only out of the country for a relatively short time. You know, it's not like I became a teenager in Eritrea, but my perspective on where I was from, I think is sort of like I'm I'm from the whole world because as a really little kid, I spent a lot of time in different parts of Africa. We were in able to travel in Asia, Europe. So I went through that long path of being in all these fantastic parts of the world and am currently back in North Carolina, which I absolutely did not expect to be where I would end up after taking detours through East Africa, South America, and Mongolia. So here I am. Um, and as far as did I always know I'd be a plant biotechnologist? Absolutely not, did not think that was gonna happen, thought I was gonna be a like professional NGO personally.

SPEAKER_01 3:01

So you moved from international conservation work with NGOs, like Smithsonian uh Fulbright Fellowship, into a PhD in plant genetic engineering. So, how did you make that decision? Was there a moment when you sort of realized that's what you wanted to do? Did it slowly creep up on you?

SPEAKER_00 3:21

Yeah. So okay, so the privilege of doing conservation stuff is that you get to live a life that is consistent with your values, right? And what I mean by that is like a lifestyle, right? Uh, like you get to often work and live in these really beautiful places you're trying to protect. And that feels like a good fit for people who really care about the environment, which I do. And so I just sort of defaulted to to those types of work. I mean, my original education didn't expect to go to grad school either. My original education was bachelor's degrees in ecology and linguistics. So went, you know, in into this conservation world, but very quickly, I would say, I got, I don't know if jaded is the right word, but I was just am I the only one seeing that this is not working? This is going the opposite direction, like just by the numbers. Like, not that I don't think we should be doing conservation work because we should, but it's like we keep doing all this stuff and we go backwards in terms of land degraded and climate change and all of that. And it seemed like that problem just wasn't, it didn't seem pressing enough in people's minds. Like, you know, we'd have to do something, like for the love of God. So, anyway, that that's sort of the mindset I was in pretty early on. And what conservation biology teaches you, which was my only relevant education at that time, is to think about land use. Like that's what the science of conservation biology is. And again, something I felt like people were kind of not paying attention to is that our number one usage of land is agriculture. About 40% of land is used for agriculture now. So then that's way more land than is protected in a conservation status, by the way. So it seemed like an obvious thing to me that like I should get into this whole world of land use for agriculture, where there's a chance to have a much bigger impact, right? To address the struggle for resources and space and all of the above. So it's a very conscious choice to make a change, go into ag. And I picked and like I made this decision when I was living in Mongolia. Like, and winter in Mongolia will is a good time to think. So it, you know, you'll start making these like big life-changing decisions. But it was that same sort of thought process we can maybe talk about in a minute that specifically led me into plant biotech out of all the ways you could choose to work on food and agriculture.

Early Plant Engineering Swings

SPEAKER_01 6:02

Very cool. And so could you give maybe a brief background on what your first projects were in plant biotech? And then eventually what led you to Elycia Bio and the projects that you're working on now?

SPEAKER_00 6:18

Yeah. So this is great. This is going very chronological, so it's easy to remember. So my first project would be the stuff that I did in grad school. And the way going to grad school went is like I showed up, I was someone who knew absolutely nothing about molecular biology or biotech, uh, and was like kind of older than other people and had a weird background, and started just wandering into biotech labs and being like, you know, I want to have massive impact. Like a lot of them, you know, sent me on my way. And ultimately I ended up working for someone named Heika Sedarov, who's a great, very creative professor at North Carolina State. And the first project that I did was trying to engineer plants in the mustard family, or maybe more accurately, the crucifers. So that's things like agriculturally speaking, it's of like canola and beets and spinach, relatively important crops, to regain a type of symbiosis they had lost, which is called arbuscular mycorrhizae. So again, if you don't know this, most plants have arbuscular mycorrhizae, like from a single origin of the colonization of land. And then in this one clade, these crucifers, they lost it. They deleted a bunch of genes, got rid of mycorrhizae. And the idea behind this project was well, now that they're crops, they could probably use those mycorrhizae again, because they're quite helpful with taking up nutrients, prominently phosphate, but really everything. So let's try to put them back. Let's see. Like it seemed like a countable number of genes had been lost. Let's stick them back in. That did not work at all, by the way. Like some of the genes did something, but it did not restore mycorrhizae. I think there's really cool work coming out of that area that other people have done. The thing that I did, I learned a lot. I did something to the plants. I did not re-engineer their microbiome.

SPEAKER_01 8:19

I love that. I did something. But I mean, that's a that is a very cool swing to take. And this is kind of what I mean when I say that you are a person of interesting projects. And so you are now working on some projects at Elycia Bio. And I'd love to hear how you came to start Elycia Bio and also tell us a little bit about how you chose the name, right? It's named after Elycia Clerotica, which is a genuinely strange and beautiful organism. And it's it's very poetic when you I think when you go into it.

Why Start Ilycia Bio And Name

SPEAKER_00 8:54

Yeah, absolutely. So the way I started the company, because I started this straight out of academia. I worked on quite a few projects over at the university, and there were a couple things that stood out to me. The first one was right, I got into ag and into biotech out of the idea that there's like power there to change the situation. And once I was in the tech world, it's like there's so much great tech that doesn't make it out into the world. Even things that look like they work. What's the missing piece? It's that generally there's more to it than just the tech itself. Like you have to go do a bunch of people stuff to turn it into a technology or a product. So in the back of my mind, there was this growing recognition that doing what I wanted probably involves some form of entrepreneurship startup thing, because that seems to be the way the tech goes into the world. And then the specific idea for this company was another one of these disconnects, which is that plant biotech is really focused on the plants themselves, right? You know, if you think about what you see in magazines and stuff, it's you know, plants with better photosynthesis, plants that are gene edited to resist drought. And that's fine. Like we should try all that stuff, but it misses a really obvious point that I came to realize is like what the plants are for, which is most of the time to feed livestock. Like that's what most of our plants are used for now, especially if you count plants that are grown on pasture, which is about three-quarters of our agricultural land. So it's I thought, well, let's take all this great biotech fundamental skills that we normally apply to the plants themselves and try to engineer plants to address the problems of livestock agriculture. And it has plenty of problems to solve. So that was the big idea. I think we've learned quite a bit about which problems make the most sense, right? And how we'll eventually get there. But that's what led me to make the jump a few years ago.

SPEAKER_01 10:54

Very cool. And tell us about the name, Elysiobio.

SPEAKER_00 10:56

Yes, that's right. Yeah. So this is a slug, a sea slug, that lives like in warm water, medium temperature water. Like you can find it off the US East Coast. And it is, if you look at it, it's gonna look basically like a leaf. It is uh transparent green and flat, like with little veins running through it. And that is because it eats algae. And the way it eats algae is that the algae it eats is like these little sort of filamentous things. And it goes to a little uh algae string, cuts the end off, and slurps out the innards, and it keeps within those innards intact the chloroplasts, the photosynthetic organelle of the algae, which it then sort of filters out into the veins of its of like what looks like the veins of the leaf, but are actually the kind of pouches of its gut. It filters the chloroplasts into the its gut without breaking them, without digesting them, and they photosynthesize in there. So it's a photosynthetic animal. And for this particular company, uh it seemed to make perfect sense. So, first of all, it's from the natural world, it matches the values of why we're doing this. Second of all, it seems like impossible. Like if you wrote this like in some sci-fi book, people would be like, yeah, that's silly. Like that's not realistic. But it's real. Like it's doing it now. And you know, it's sort of it's about the interaction between plants and animals, which again, like our with this with the original livestock feed idea, the first trait that we made was drawn from seaweed. So this is literally an animal that eats seaweed and it does this magical thing. So it's there are all these parallels I just loved. The problem, I'll tell you the two problems with the Lysia, the animal. The first one is it sounds a little bit like my name. So people will ask me, like, who's Lisa? Oh, like, because they sort of think I did like my wife's name or something, and we then it's not. And then the second is it does another thing, which LinkedIn must never get a hold of, which is that separate from the photosynthesis stuff, the slug gets parasites, like all animals. And when it gets too many parasites, it amputates its entire body, and the head just goes off and grows a new body, which is like way too on the nose for like business bullshit to be allowed out into the world for LinkedIn to hear about.

SPEAKER_01 13:35

Well, we may post this episode on LinkedIn, so hopefully the LinkedIn AIs are not crawling into the episode. Fascinating. I love a good poetic name. And I also love the journey that you know that you went on from you know wanting to save the world, or you know, wanting to protect nature, and eventually moving into a very specific problem, animal agriculture, and we'll get even more specific about the problems that you're dealing with. And uh that I think is a pattern that a lot of people experience, right? They're like, okay, I want to address climate change or I want to address biodiversity loss. And the problem is so big that you eventually have to go on down this road of finding really what you're actually going to work on so that you can find something that like is really addressable. Because it's hard to work directly on climate change, right? You have to when you go into the lab every day, you are not working on climate change, you are working on some very small part that you've identified is an important lever. And so maybe now is a good time to talk some specifics about what you're cooking up at Elycia. Tell us, like, tell us about the yeah, about about your goals.

PLAMO And Atmospheric Methane Oxidation

SPEAKER_00 14:52

Yeah, so so we do we kind of work on multiple fronts within that big idea of feed crops that are engineered to solve livestock problems. And I'll try to explain where the multiple fronts come from. So the very first place we started was can we engineer feed crops to get rid of something called enteric methane, which is like a fairly prominent topic now. This is methane that comes from ruminants in the rumen, the first of the four stomachs. It's produced from the fermentation by microbes of the plants that the animal eats. And basically, before the animal can get to it, a portion of that of those plants are fermented into hydrogen and CO2 and then re-fermented by different microbes into methane, which is then burped out. And that is the single largest source of methane on earth, like you know, which it doesn't sound like it should be, but it is like bigger than oil and gas. And that automatically makes it a big environmental problem because it's methane, and I'm not gonna like dwell on why we care about methane, but like because it's methane, there's a chance for a rapid impact. So that's good. And then on the livestock side, like my perspective, because I come from plant biology and I trace the carbon like from the CO2 in the air into the plant, into the animal that eats it. I'm like, okay, this is just a bug in the process of turning plants into animal products, this loss of methane. It's a leak. So if we plug the leak, we can also probably make the animals themselves more resource efficient, which is both a commercial benefit and it further increases the environmental benefit, right? Because if you don't just stop the methane, you probably make the animals a little more productive on the same amount of feed if you get that conversion. So the first big idea was we're going to produce this small molecule called bromaform, which comes from red seaweeds, which again in the methane world were very popular at the time I started the company. We're going to take that, figure out how to genetically engineer it, and put it into a feed crop starting with corn that would then go to livestock. And the appeal to farmers compared to like the seaweed itself or the drugs and additives that are out there is that this is easier to use and frankly cheaper, right? They already feed corn to cows. They don't have to do anything different. We just get rid of the methane. That works, by the way. Like we that trait was relatively easy to engineer. Uh, we have it in corn now. But what we learned and what led us to now have several other approaches that help us get at the full scale of the problem are first of all, like simplest and most obvious, no one crop will work for every livestock, right? Not every cow in the world eats corn. And in fact, the ones that most need our help are the ones that don't. Because if a cow's eating corn, it's like on a farm somewhere and you can probably give it a drug for this, right? You know, maybe our corn is cheaper or better, but it has options. But that's less than 10% of ruminant livestock are on farms like that. Most of them are on pasture, some form of pasture. They're outside small farms, they can't easily take a drug every day. And for them, we can have much bigger impact because they have very few other options to get rid of these emissions. Um, and they also are in food systems where their role in the food system is much, much harder to replace, right? So to reach those animals, we need to be in different plants that work for different types of animal feed. So pasture grasses, different types of hay and silage. So we've moved beyond corn into different types of plants that help us target much more diverse farming systems. So that's kind of expansion number one. Expansion number two was looking beyond that one molecule, which is probably not the single ideal molecule for every single setting for both like technical and acceptance reasons. So we look at other ways to get rid of methane using plants. The simplest way is other molecules that suppress enteric methane, which we have, right? You can go read about tannins and terpenoids and quite a few things in nature that are decent methane suppressors. But it also led us to something we call the PLAMO project. And this was us asking if instead of preventing methane from existing, could we allow methane to come into existence inside a cow gut and then recapture it and turn it back into a useful form, one that is bioavailable to the cow. And I love this idea for a few reasons. One of them is it really gets away from the ways people have thought about the cattle problem before. It gets into all of this amazing knowledge that exists about methane biology, right, in microbes, right? If you go read industrial biology research, there's a big interest in using methane like from factory flus to turn it into something useful. And it seemed like we could tap that to apply it inside the cow, right? So one of the first ideas was could we just take microbes that consume methane, methanotrophs, and feed them to a cow? There, there's a group in Korea that did that and saw a 10% methane reduction on their first try, which is pretty good. But then you still have the problem that you have to feed something constantly to an animal. And so that brought us back to saying, well, do we know what in the microbe is responsible for making methane not be methane, burning it into something else? We do, the enzyme called methane monooxygenase. And could we take that enzyme and instead express it in the plant? And and I like, I know like separate you you know about this project, but so I'm laying it out chronologically. The origin for this project was very focused on the cow. Like where this all still is about something that happens inside a cow, where we have, you know, fresh grass loaded with methane monooxygenase enzymes that a cow eats, they go into the gut, which is very high concentration methane, convert that methane into methanol, which is the first product of the enzyme, and then with some complementary enzymes, turn it into a bioavailable form. That was the first thought. And we ultimately, as far as the cattle site, set that aside for after we first thought of it, because it was really complex. It was a really tough enzyme. And it seemed like we had some easier routes to cattle impact, but we revived it basically for an even bigger idea, which is what if we didn't have to feed it to the cow at all? What if the plants just took methane out of the air? And we kind of realized well, if they work. If the enzyme worked, there's no reason it couldn't, right? Any methane molecule that found its way into the plant tissue would be oxidized by the methane monooxygenase, turned into methanol. And within a plant, which is a little different from some of the challenges with people trying through something similar in microbes, methanol is fine. Like plants are full of methanol. They have a way to get rid of it. So just get reincorporated to biomass. So this, that project, we ultimately decided to push forward on it a couple years ago with support from Spark Climate, which is a methane-focused grantor, have been able to push through a huge volume of plants engineered with different forms of methane monooxygenase. And literally just today, so this is well timed. Oh no, it's not that exciting. But literally just today, we have begun running the analytical chemistry analysis that give us basically a an incontrovertible yes-no answer on whether we get methane oxidation out of these. So that last project spent a little extra time on it because it is like at this very exciting point that we're quite interested in.

SPEAKER_01 23:05

Very cool. And so that there was a lot that you just shared. And so I want to try to recap. And that methane is the largest source of methane on the planet. So it's a major pollutant. Methane is 80 times as strong of a greenhouse gas compared to CO2 on short timescales, and and about 20 times as strong at a 100-year timescale. And so methane is a big deal and accounts for about 30% of climate change, just for the context for listeners. And bromoform is this chemical in red seaweed that can inhibit production of methane. And so you thought instead of having to feed cows seaweed or purified bromoform, let's put it directly into the food that we are feeding them. And then you started producing or you started also approaching that problem from other angles, which is where you got into methane monooxygenase, this enzyme that oxidizes methane, which basically means it reacts methane with oxygen. And you wanted to do that process in the cow's stomach by putting that directly into the feed. And then eventually it got you to this atmospheric methane removal idea as well, where if MMO, this methane oxidizing enzyme, is in the plant, then why can't it also just remove methane from the atmosphere? So that did I get all of that right? Yeah, uh-huh. Thank you. Perfect. So very interesting, fascinating. So at homeworld, we love so let's talk about some of the challenges in here. So at homeworld, we do our best to focus on the problems we need to solve to de-risk potentially high impact technologies. And this is a really potentially high-impact technology, and there's some challenges associated with getting there. I know MMO is a very challenging enzyme, and there may be also some other unknowns around you know, how much of this enzyme do you have to produce in the plant? Like, if you are producing this enzyme, is the plant gonna still be able to grow at the same rate, or is it are you gonna get a yield hit? So these are all things that you'd want to sort out, right? And I think you you have a paper coming out soon that addresses some of these de-risking problems, and then some of them are kind of more on the like technical de-risking of actually expressing a functional MMO in the plant, right? So maybe we can talk about some of those challenges.

SPEAKER_00 25:33

Yeah, no, so the real challenge for the like incredibly smart people that have been working on biological methane oxidation for a long time, is that there is no reliable transgenic expression system, which typically, if you want to understand like protein function and make them better and so on, that's what you use. So you use E. coli. You say, oh no, it didn't work in E. coli, we use yeast. Well, it doesn't work in any of those, right? So there's like a backlog of great ideas from amazingly smart people who studied this protein. We haven't been able to test them to figure out even the exact details of how it works for sure, because we don't have elegus systems.

SPEAKER_01 26:17

And a heterologous system would be expressing methane monooxygenase in an organism other than a methanotroph. Yes. It comes from these methanotrophs who eat methane and use MMO all day long to oxidize methane, but then we try to get that enzyme in other organisms, it doesn't work.

Building The MMO Research Community

SPEAKER_00 26:36

Yeah, and I would extend that a little bit a heterological heterologous system of interest is like one where the enzyme also works a little bit. Like we can we could make MMO briefly in E. coli before it dies, but the enzyme won't work. Or you could probably make it, you could make the protein components in a cell-free system that won't suffer from toxicity, but it won't fold right or it won't have a membrane to embed into. So again, it won't work. So it's been really challenging. And, you know, that's it's a tough thing to beat your head against the wall on. So part of the interest, right, that made us think there really was some potential here is that, you know, the ultimate draw is about the scale of plants, right? They're very scale, very cost-effective, etc. But there were some hints that plants might happen to be a decent heterologist system for MMO enzymes from a couple of academics that had worked in the space. Stuart Strand, who unfortunately passed away recently, was a professor at West Virginia, and Verena Kriegbaumer, who is a professor in England, had done some pilot experiments and shown that you can express these enzymes in plants. You can find the protein, they seem to fold and assemble correctly. Maybe a hint of activity in some of the work from Professor Strand. And relative to the challenges we've had with microbial hosts, the fact that relatively modest attempts gave us these little promising hints, look promising to me. And that's also what led us to uh just dive into the idea of saying, well, maybe this host will give us an option to break through some of the technical problems. And right, we're about to find out if it will. I can tell you, we have seen, because we've looked at it pretty closely, that MMO, both particulate and soluble, are still tough. We use gene sequencing to look at expression levels, and we can see that compared to a typical gene that you would heterologously express in a plant, these things don't get to the same high level. They're being silenced or expressing poorly. So there is some pushback against them. And right, we've done work on that to try to fix it, to try to push the expression up, because you know, as you alluded to at scale, we think through this modeling work we did that will be published soon, that there's a fairly linear relationship with the amount of this protein you could make in a plant to its expression, or the expression of the amount of protein you can make in a plant to its actual impact on methane oxidation. So, in the long term, if we get early hints that this works, that's going to be the next big challenge is really trying to push the expression up. There are questions about where in the plant to put it, questions about access to some of the cofactors. So it needs some metal, it needs a source of electrons. So all of those feed into the equation. Our approach, so we put in quite a wide variety by plant standards, maybe not microbial, of different versions of this enzyme into our plants, with the idea of testing different versions to try to find out one that points us in the right direction. And increasingly, the approach that looks like it works is what we call rationally engineered proteins. So this is where we used our human brains and like our broad understanding of how proteins worked, and did some redesign on the protein and stuck it to other components, not from MMO. And the early hints we have is that it's those candidates that may in fact have some activity.

SPEAKER_01 30:19

And it's worth maybe pointing out here that Homeworld has a couple grantees that we've supported to work on problems related to methane monooxygenase, which were actually inspired by problem statements that you helped write, Eli. We had we've discussed this in some previous podcast episodes, one with Lauren Luger, one with Sam Abernethy, but Homeworld and Spark Climate Solutions hosted this workshop on atmospheric methane removal. And we were talking about what were some of the actionable problems for helping to speed up the, you know, our ability to heterologistly express MMO. And two of the big challenges that came out were number one, understanding the actual biophysical environment that MMO operates in methanotrophs, because it's sort of curious that we can express the enzyme in other organisms, but then it doesn't work. So there's something about the environment in the methanotroph that's important, and this has never been measured before. And then, you know, we put that problem statement out in the world, and Michael Kanopka and Lauren Luger responded to that. Michael Kanopka studies methanotroph membranes, which host the particulate MMO. And Lauren Luger develops fluorescent biosensors and has developed a host of fluorescent biosensors for detecting various biophysical parameters and molecules in neuroscience. And they are adapting those sensors to sense the biophysics of the membrane where MMO works in methanotrophs, looking at pH, redox, voltage, a bunch of different ions, including copper. And the other one was this challenge of actually measuring methane oxidation precisely and quickly. And we put a problem statement out in the world on that topic as well. And Douglas Call, who is work professor at NCSU close by where you're working in Raleigh, Eli, responded with this very interesting electrochemical assay that he developed to measure redox proteins. And so and Homeworld was able to give him a grant for that as well.

SPEAKER_00 32:36

I feel like it's right, it's separate from like the specific grants, there's community building effort. I was actually like it was a little bit of a shock to realize that the workshop that fed into the report was in 2024. Like feels like forever ago. But like there's like as I'm seeing it, there is this conscious effort to try to build up some connections, which is great, right? Like I I don't come from the world of ethanotrophs, and like have been able to meet some people that are basically the world experts on that, and then bring to them some things that we know because methanotrop people don't normally deal with anything to do with plants or our type of engineering. And then, right, same, right? Doug call, you know, electrochemical enzyme activity could apply to anything. Now he's applying it to methane. And to make that work, he's gonna need a source of enzymes. So like we're collaborating with him to try to share some material. He's also working with some of these experts. So there's a little bit of a wave, which I feel like you guys were intentionally trying to build up, which is great. So good work. Yeah, like and even beyond those people, some of these little events that that have been held, like it's they've been super helpful, right? I know we're we were just talking to the folks at Spark, trying to think about what comes next for some of this tech. It's good that we have that kind of network and set of people that are potentially part of what does come next.

Business Model Without Carbon Credits

SPEAKER_01 34:04

Absolutely. I mean, this is what homeworld's about trying to help people come together, collaborate to de-risk potentially high impact technologies. So it's very exciting to see it in action with this with all of this MMO work. So taking a step back now, we went deep into the weeds. So I'm curious from the business model standpoint, engineered plant-based methane removal sits in sort of a unique position relative to both the egg biotech and carbon removal or greenhouse gas removal investment landscapes. So how are you how are you thinking about where Illycia fits in here? And like who do you envision your early partners or customers would be?

SPEAKER_00 34:49

Yeah, the carbon removal side of this is really brought, right? And the big story right now is that, well, like the new administration is anti-climate and are gonna take away incentives. But I go back to my environmental experience that you know, carbon credits probably do something, but they have a checkered history, right? We made a lot of mistakes there. And the ideal is if you can make something pay for itself without carbon credits, like that's the benefit. And that was part of what brings us into plants, which is that one half of that equation uh for plants for almost anything looks really good, which is being cheap, right? So to pay for yourself, you need to make more money for the people using it or whoever's pushing it than it costs to do. And so when we're deploying something in a crop plant or a forestry tree, the benefit is that we're already planting those plants, we're already planting the trees. So a lot of the economics look really good if we can sort of be a passenger with this existing process, as opposed to write some other great technology that starts from a place of, well, we're gonna have to build a fermenter. And so you start with a relatively high cost. So we can come in at a pretty low cost, ease of adoption is good because again, it's basically people doing the same thing, same thing they're already doing, but the other half of the equation, right, then is why are they doing it? If there's no carbon credits, like if we choose not to depend on those, there has to be a different motive. And you know, again, but some of the other answers to that are ones that are very fraught, like the government makes you, probably not a good idea. You're convinced to out of the good of your heart, they would love that, probably not a good idea. And we connect efficient or we originally thought that would be actually the big root for methane, which is what we turn the methane into, has a role in plant life, so it's a signaling molecule.

SPEAKER_01 36:50

So we're getting close to the end, and like synthetic biology in plants is known to be quite challenging compared to synthetic biology and like you know, microbes, like E. coli. How has that shaped your design choices at Ilysia and what kind of challenges, you know, do you face as a result of that? And on the flip side, what are some challenges in plant synthetic biology that like could unlock productivity across the whole field?

SPEAKER_00 37:17

So it's a good question. Uh, and I think basically I just fundamentally disagree with the idea that it's harder in plants than microbes. So I'll give you an example. So let's say that the thing you want to make is anthocyanins. So the anthocyanins are very common purple pigments, like they're what's in blueberries and cherries and all of them. So let's say you're trying to make anthocyanins. And let's say that you have two organisms you want to make it in. One of them is E. coli, one of them is sweet corn. And by the way, if you've talked to me in the past, I come back to purple sweet corn often as an example. So this is that again. But so, all right, so you want to make anthocyanins in E. coli, you're gonna have to put a 20-gene pathway into the E. coli. And sure, putting a 20-gene pathway into E. coli is easier than putting a 20-gene pathway into plants, like time-wise. But in plants, you can do it with one gene, right? Because plants already have the ability to make anthocyanins. Almost all of them do. So take one little gene, plop it into corn, turn on the natural anthocyanin pathway, and you'll get your purple corn. Like I've literally done this for fun with non-corn plants and made purple seeds with a single gene. So I think it's that there's different applications, right? Like, and what I'm always fighting for, and why I tend to be kind of forceful about this, is I don't think we should default to the idea that synthetic biology always has to start in like I think we need to expand the pantheon of hosts to ones that look like a good fit for a certain job. And if we do, right, you know, give plants a chance, and there's certain jobs that they're gonna be really good at. And right, and I think that's what we live every day. You know, there's like when you talk about plant plant synthetic biology worldwide, there's a very expensive drug which is made out of South American tree bark. This is a pharmaceutical super high value made through modifying a really complicated natural molecule, which is only found in this tree. So in South America, there is this little cottage industry of farmers growing trees and extracting their bark and sending it off and it gets processed. And people have always been bugged by that. Because you need a huge amount of tree bark to get enough to make it like one pill. And there is a there was a recent breakthrough, I forget who published it, but where they're able to do most of that long biosynthesis pathway for the molecule in a microbe. They got it in with the idea that then you won't need the trees anymore. And I've always, by contrast, well, this would be a great case to work with the tree and see if you can make you know a hundred times more of this chemical with a smaller set of genes, but with a, in my view, an easier production system with this tree that's already built to make this chemical. So I'm really curious watching that example, because now we have head-to-head race, right, between someone trying to achieve it with microbes and then people that one would hope are trying to achieve the same thing with plants with constant improvement. But I would see a great case for all of these high-value natural products that already come from plants, but which would be hard to engineer in microbes, where we should at least try. Like try to make it better in the plant. And I think too often we don't even bother to try. Like, I think we get huge results in in a lot of these cases.

SPEAKER_01 40:42

Would this result have happened to have been from Maria Astolfi?

SPEAKER_00 40:47

I would have to check.

SPEAKER_01 40:49

QS21.

SPEAKER_00 40:51

Yes.

Rapid Fire Favorites Advice Hot Takes

SPEAKER_01 40:52

Yeah. That's so cool. Homeworld actually funded Maria to do some of that work. So funny to and just beautiful to see it coming up. Small world. The Climate Biotech podcast is powered by Homeworld Collective, a 501c3 nonprofit unlocking biotech solutions for planetary health by fostering community, building knowledge, and directly supporting early stage research. We are always looking to connect with scientists, innovators, and funders who want to accelerate progress in this space, whether in our current programming areas of critical minerals and greenhouse gas removal, or in other application games. If that's you, reach out to us at hello at homeworld.bio. So, okay, so a couple more stereotyped questions here. So do you have a favorite organism?

SPEAKER_00 41:43

So I'm very hard for me to pick a favorite, but the one I've been thinking about today, really easy, is elephants. I think elephants are great. They're like there's they're like the perfect balance between like intelligent and relatable, but still like an animal with a very alien life to us. Like if you've been around an elephant, it makes you feel something.

SPEAKER_01 42:07

Very cool. And w what's a s what is a book or paper or art piece or idea that blew your mind and shaped your development as a scientist?

SPEAKER_00 42:18

Oh, yeah. So all right, so this really sticks with me. It's the really simple thing that if you run a DNA gel, like gel electrophoresis and you get a band, you can cut the band and get DNA back out of it and do something with it. And I've never gotten over this because like most people, like if you're in school and you run a gel, you think of the gel as data. Like you did a PCR, did the PCR work? That's what the gel tells you. So it's data. You can turn data back into physical material and put it in a plant, and then it'll do something, right? That just it doesn't seem like it should work. You shouldn't be able to take a knife and cut the band and have DNA in there that you then go and work with, right? That that like that, I don't know. That's it's like on a list of a few things, fusion proteins among them. It's like they shouldn't work in biotech, but they do, and that's why I like. Very cool.

SPEAKER_01 43:09

So, best advice line that a mentor gave you, is there any wisdom that you would like to share that you learned along your journey?

SPEAKER_00 43:18

I'll make this fairly targeted to people doing like plant and ag related work. I have a guy who's on my graduate committee who brought me into NC State. Parts of why I chose to go here. His name is Fred Gould. He's a very well-respected researcher of like biotech ethics, and his scientific specialty is genetic pest control, which includes simple things like you know, BT corn and like some of the like biggest questions you could imagine, like gene drives, where you drive a species extinct. And I was like attracted to the power of the tech that I was seeing through things that he'd shown me. And so I was like, okay, I'm gonna go to school near you. And so I signed up to go to grad school, showed up, and I asked him, having committed to study biotechnology, I showed him, I was like, well, what like what's your one piece of advice for like what I should focus on and like really keep in mind, as I said to me? And he said, well, you know, anyone who comes into my lab, I feel like they need more ecology. And I'm like, Fred, I just quit ecology to do this. So now you're telling me it's more ecology. But Fred was right that like if you are a biological inventor, if you're a biotechnologist, and you invent what I think is interesting, which is biotech that can go out and live in the world with us, right? And we didn't even get into why like plants over microbes just for their relatability. But if you're gonna be willing to understand the world they're gonna live in, like this is a living thing that lives in the world and has interactions with bugs and microbes and pests, and that that stuck with me, right? So I think if you are in biotech and you're a really creative person, you gotta see the application you're working with as a complex, real life ecological thing instead of trying to turn it into something that looks more and more like a chemical.

SPEAKER_01 45:11

I love that one. That's good advice. Okay, if you had a magic wand to get more attention and resources into one part of biology, it can't be investment to Elycia. What would it be?

SPEAKER_00 45:26

So I again I would say gene synthesis and appreciation for what has changed in gene synthesis lately, but it has gotten much cheaper, largely thanks to a company called Twist. And now at a point where having a gene synthesized off you know biotech bioinformatic knowledge on the internet, it's almost always cheaper and more convenient than going out and finding the organism and like extracting its DNA and running a PCR. And that's only happened in the past few years that we now source our DNA through the internet in a physical sense. And it's the same reason I like the gel. It's like we're turning DN, we're turning data into reality. And I think there's another Rubicon to cross, which is if gene synthesis gets roughly 10 times cheaper than it is today, right? And it's done that before, so it should do it again, and a little better in some very concrete ways, like better at doing repetitive sequence, longer fragments, we'll get to the point where it can displace a huge number of things we spend time on in the lab, like cloning and like a bunch of PCR steps, a bunch of error. And if we achieve that, right, we almost directly affect the like manifestation of the idea physically to the computer, to like to your ability to exchange ideas. And like I think we can't get there soon enough. Like I actually I like cloning a lot, but I will happily give it up like if it if we can make it this much easier to just design idea and and go in biotech.

SPEAKER_01 46:59

Very cool. Okay, now I'm gonna ask you for a hot take. What is one view that you hold related to climate and environmental biotechnology that you think some others in the field might disagree with? And you already said one, which was that you questioned the difficulty of plant engineering relative to microbial engineering. Yeah. Is there anything else you wanna you wanna give us? Anything else spicy?

SPEAKER_00 47:21

I think CRISPR is overrated. That's my latest hot take. And it's not that it isn't great, but uh I think we have lost sight a little bit, even really smart technical people, of how much of the excitement about CRISPR had to do uh with like public relations and regulatory. Right? Yeah, I tend to think plant first, but a ton of the excitement about CRISPR for ag was that at least in the US, it was way easier to get through regulation than than classic transgenics. And so fair enough to be excited, but we have conflated that with the idea that CRISPR can do anything. And there's quite a bit in a molecular sense it can't do. When you read about like a lot of the latest exciting stuff with CRISPR, it's usually combined with several other biotech methods. And we never attribute it to those other biotech methods. But but like so it's just like CRISPR just feels the limelight for something that like, you know, you may as well have just said gene insertion if you're inserting like a fragment with homology arms alongside your CRISPR. But we always call it CRISPR if it touches CRISPR.

SPEAKER_01 48:29

Okay, and our final question for our listeners who are on their own journey in biotechnology, what is one aspect of personal development that you think people working in the climate and environmental biotechnology space need to spend more time on or just you know, invest in themselves?

SPEAKER_00 48:51

So I I think it is you have to break out of typical institutions. Like and usually for most people that's gonna mean a university or it might mean a company. And I think like we've touched on a couple other times, part of what I liked about biotech is it's easier than people think. Lots of things are happening that make it more democratized. And I think you become a better scientist if you like admit to yourself that you can practice your art outside of a very constrained academic or corporate setting. So people should go seek out, you know, these like DIY bio groups, uh Biopunk house just started up over in San Francisco, Sound Bio in up in Seattle, a bunch of the biohackerspaces in Boston, like they're out there. There's one in Durham called Splat Space, where I started my company. Like those places are there and they're very freeing for your mind if you can break out of the mainstream system.

SPEAKER_01 49:58

Very cool. All right. Well, Eli, it has been a pleasure to speak with you today, as it always is. You've had so many, I mean, your journey has been fascinating. The technologies that you're working on are fascinating. You got some great, interesting nuggets to share with us. Thank you so much for taking the time to speak with me today. And I look forward to you know continuing to think together and work together as part of this wave of folks trying to make MMO technologies happen. Awesome.

SPEAKER_00 50:28

It's always nice seeing you.

Closing And Where To Connect

SPEAKER_01 50:30

All right, right on. Thanks for tuning in. I hope this has been educational and inspirational for you as you navigate your own journey to bring the best of biology into planet scale solutions. I'll be back soon with another conversation. In the meantime, you can stay in touch with Homeworld on LinkedIn, X, or Blue Sky. Huge thanks to our producer Dave Clark, along with Paul Himmelstein, Caleb Sims Austin, and Cario Sarzozo for making these episodes possible. Until next time, I'm Paul Reginato, and this is the Climate Biotech Podcast.