The Climate Biotech Podcast
Are you fascinated by the power and potential of biotechnology? Do you want to learn about cutting-edge innovations that can address climate change?
The Climate Biotech Podcast explores the most pressing problems at the intersection of climate and biology, and most importantly, how to solve them. Hosted by Dan Goodwin, a neuroscientist turned biotech enthusiast, the podcast features interviews with leading experts diving deep into topics like plant synthetic biology, mitochondrial engineering, gene editing, and more.
This podcast is powered by Homeworld Collective, a non-profit whose mission is to ignite the field of climate biotechnology.
The Climate Biotech Podcast
Solving for the P in NPK Fertilization Using Enzymes with Benjamin Scott
The global food system has a phosphorus problem that few people talk about. Unlike nitrogen, which cycles naturally through our atmosphere, phosphorus is mined from finite deposits and has no natural cycle. A massive 100-kilometer conveyor belt—visible from space—transports phosphate-rich rock from the Sahara Desert to ships waiting to distribute this critical resource worldwide. Any disruption to this supply chain would threaten global agriculture, yet when phosphorus runs off fields, it creates devastating algal blooms in lakes and rivers.
Ben Scott, Engineering Biology Platform Lead at the Global Institute for Food Security, is developing an elegant solution using protein engineering. His team is redesigning enzymes called phytases to unlock organic phosphorus already present in soil but unavailable to plants. Up to 80% of organic phosphorus exists as phytate molecules bound to metal ions, making them inaccessible. While natural phytases can break these bonds, they've evolved to work in acidic, warm environments—not the neutral, cooler conditions of agricultural soils.
Scott is combining protein engineering with automation and AI to create enzymes specifically tailored for field applications. His team uses high-throughput robotics to test thousands of enzyme variants across different conditions, generating quality data that feeds AI models to design better proteins. Through this, accomplishing twin goals — reducing our dependence on mined phosphate while preventing the environmental damage caused by phosphorus runoff — could be within reach.
The work exemplifies how synthetic biology can address climate and food security challenges through creative biological design. By moving beyond the limitations of natural enzymes to create proteins specifically tailored to agricultural needs, Scott's research points toward a more sustainable future for phosphorus management in global agriculture.
Ben Scott on LinkedIn: https://www.linkedin.com/in/benjaminmscott/
There is a 100 kilometer long conveyor belt that you can see from space that is simply built to transport phosphate containing rock from the middle of the Sahara desert to the Atlantic Ocean and that is then distributed around the world. So there is a huge supply of this rock. It doesn't look like we're going to be running out anytime soon, but if there was a disruption to that supply in the middle of the Sahara Desert, we would have some serious problems around the world because of the finite necessity of phosphate fertilizer.
Speaker 2: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. We're thrilled to welcome Ben Scott for discussion about climate biotech. Ben is a rising star in the field of protein engineering. As the engineering biology platform lead at the Global Institute for Food Security in the University of Saskatchewan, where he directs the state-of-the-art biofoundry for multi-parametric design and screening of enzymes, ben's work is right at the interface of protein engineering, ai and automation. Ben's work is right at the interface of approach engineering, ai and automation.
Speaker 2:Today, we're going to talk about his deployment in the context of unlocking phosphorus in soils. Oftentimes we think about fertilizer for plants, we're thinking nitrogen, but what we're forgetting is that phosphorus is just as important and actually has some very big insecurities behind it that we need to consider. In this topic, we're also going to discover Ben's history in synthetic biology, including helping yeast see. Prior to the Global Institute for Food Security, he was working at Concordia University and the National Institute of Standards and Technology here in America, having led projects spanning from human therapeutics to agricultural enzyme, ben is recognized and appreciated for his computational design, work with robotics and using the synthetic biology design, build, test, learn cycle. That's a lot of words and we can't wait to get started, ben. We're thrilled to have you today. Ben, who are you and where did you grow up?
Speaker 1:Thanks, Dan. That was a lot of words and hopefully some of that will stick with the audience. There's a lot of different directions that my career has gone and so fun to hear it put into words. So where did I start? I grew up in Stratford, Ontario, which is known for its Shakespearean theater and actually surrounded by farms, so it's also the pork capital of Ontario. But honestly, for me it was a very kind of small town life. I was not exposed to agriculture directly much other than to visit a farm. So yeah, I'm actually relatively new to the ag space.
Speaker 2:Wow, and did you always know that you'd be a leader in protein engineering and lab automation?
Speaker 1:Definitely not. I had no idea what protein engineering was or lab automation, until really into grad school, I would say. So I started out as a lot of kids do you're interested in science, but you're not really sure what else you can do with it. So I started a general kind of life sciences degree, thinking I might go to med school human physiology. I took a course in that in undergrad and it just raised more questions. It was like talking about how the nephrons work in your kidney and how your intestines work. But the story would stop there and I got really frustrated that I didn't really get taught or understood what happens actually at the tissue level and it turns out it's proteins doing a lot of that work. So that's what led me to eventually getting into some protein science research.
Speaker 2:Yeah, it makes me think exactly why I dropped out of bio in my undergrad too. It just felt like it was taught like geography. Right? It's like, yeah, I've memorized. This is next to this. All right, let's move on to the next topic. And there's no foundational things to build on top of each other.
Speaker 1:Yeah, oh, exactly, it's like learning geography without history. It's like understanding, oh yeah, okay, these are the borders of the countries and all of that, and that's where they are, but having no context for why there is a border there or why they speak that language there. Yeah, it was not enough for me.
Speaker 2:Perfect. So what was the mapping then? What's the first experiment you did?
Speaker 1:The first experiment I did. I got incredibly lucky to land in a lab that looked at my experience in undergrad and said, yeah, sure you can pick up a pipette, when really I hadn't done a whole lot of that. So my first experience was putting a couple of pieces of DNA together and then expressing a protein with that. I had some beginner's luck. Honestly, like it all worked and I thought to myself why is this difficult? But it turns out that was the first and probably the last time it worked that easily for me. But I was hooked. I really enjoyed it and I had a lot of fun in that lab.
Speaker 2:Nice, and this was your first year of your PhDs in time.
Speaker 1:So back in my undergrad actually. So I did a fourth year thesis project. This was at McMaster University in the laboratory of Bill Sheffield. I'm actually reconnecting with him tomorrow. I'm actually really excited to reconnect with him. That's awesome. So you got to work in Bill's lab for your fourth year and then what made you continue on with biology? He was doing, and still is doing, some really great stuff with protein engineering, and there was no other place at my university that was doing that type of research and that led me to a full fledged career in protein engineering. In that case, that was for medical applications, so designing new blood thinners. There's lots of cool ways that our body regulates how our blood clots and dissolves those clots and, yeah, I loved it. I couldn't get enough of it.
Speaker 2:And so you had the choice probably to go to industry for a little while after undergrad or continue on. Where did you go, and why?
Speaker 1:I never, honestly, I never considered it Maybe financially for financial reasons I should have because grad school.
Speaker 1:You don considered it maybe financially for financial reasons I should have, because grad school. You don't choose grad school for financial reasons, that's for sure. But after my master's. So I continued and did a master's with in Bill's lab. I had a great time, but I wanted to learn something different and I wanted to leave the city, if nothing else to find different life experiences. Hamilton, ontario, is a great city. I wanted to just try somewhere new.
Speaker 1:I thought about going overseas because I knew that synthetic biology was taking off in the UK. I had some family in the UK and I thought, okay, maybe that could work. And then this professor at U of T so in Toronto, they said that they do synthetic biology and that was enough for me and I'm like, okay, great, there's at least one person in Toronto, one person in Ontario, canada, that is doing synthetic biology. I'm going to join their lab and I did. And that led me to doing a PhD, which I also had a blast Again protein engineering for therapeutic applications.
Speaker 1:Those projects during my PhD were looking at cell surface receptors. There's a family of those called GPCRs or G protein coupled receptors, major drug targets. But it turns out you can also engineer them to sense the cellular environment. That work eventually led to engineering a yeast that is able to sense gut inflammation and then delivers a anti-inflammatory protein in response to that signal, and that all it's all been published. So I'm happy to talk at length about that. But that that was a really, I'd say, truly synthetic biology.
Speaker 2:It's not just protein engineering anymore yeah, that's really cool, and if you fast forward from maybe one or two labs a decade ago to now, you're a part of two very cool organizations. So there's now SynBio Canada and the Global Institute for Food Security, so I'd love to just hear a little bit about both.
Speaker 1:Sure, I started Symbio Canada during my PhD because I knew that there had to be other people out there that were as passionate about this. I just thought it was so cool. I knew that there were other organizations like Symbio UK and the EBRC in the States a variety of other organizations, but nothing in Canada and I thought I'm just going to buy a domain online called Symbio Canada and see what happens. That was essentially my plan and it eventually was a great career move in hindsight because it led to a great ability to network, build connections. It's now I think we've got two or 300 members now across the world we don't just limit it to Canada Really proud a few hours that I put in to initially buy that domain and then many hours later of webinars and connecting with people. It's led to something cool.
Speaker 2:Yeah, I got to riff on that for a second, because that's a big motif in my own career, right? Is that networking has such a bad LinkedIn overdose connotation, right? But if you think about it, the essence of that is finding people that are working on very similar things, that are geeking out with you on the hallway, and a little side comment from someone on something that might be published in a few years ends up becoming a collaboration, and I think this is why I think it sounds like both SynBio Canada and Homeworld Collective has spent so much time thinking about just trying to engineer those moments of critical mass.
Speaker 1:And it's so rewarding and I'm sure you've experienced this too Like you'll make those connections and you never really. You put those two people in a room or whatever and you walk away like, okay, that's great, that they had a nice conversation, and then you see them five years later and they've not only gotten a great job as a result of that or went off and did this fantastic project. It's really cool.
Speaker 2:Yeah. So I want to get to FITASES because I think what you're working on is so cool and I should say Homeworld Collective is thrilled to be able to support your project with the garden grants and seeing all the cool work you've done so far, I would love to just lay a little bit more groundwork, which is to introduce the Global Institute for Food Security, and then also touch on some of your previous work. The yeast project, for example, is super cool, but let's just talk about those a little bit and then segue that into phytase is to know why you chose that. What is GIFs?
Speaker 1:Yeah, a very unique, very special place to work. I've fully admit I've drank the Kool-Aid. It fully convinced me that this is a great model. It is a research institute at the University of Saskatchewan, so it's affiliated with the university. It's not independent. We do have our own board of directors. We do have our own ability to generate our own intellectual property that is somehow separate from the university, and so there's for anyone who's dealt with a university tech transfer office, you'll know that's a huge benefit to be able to do that. And we are also able to source our own investors.
Speaker 1:Farm Credit Canada, which is essentially a bank for farmers, has invested in the Global Institute for Food Security because they see the value of funding discovery-driven as well as application-focused research as a direct value to farmers. Our mission is to ensure that everyone has access to safe and secure food. Our mission, rather, is to work with partners to discover, develop and deliver ways to do that. So it's all about being that bridge between academia and an industry application. And if you're familiar with the valley of death, when you have something in academia that you've discovered, well, how do you actually commercialize that? There's a lot more work that needs to go into that, and that's the sort of space that GIFs plays in that, believe it or not, the valley of death.
Speaker 2:And so this is going to be a two birds with one stone question. Had you worked on anything non-mammalian before you went to go work at GIFS?
Speaker 1:Lots of stuff, non-mammalian, nothing. Some experience with, I'd say, metabolic engineering, so for industrials kind of stuff, but nothing ag related, nothing plant related and nothing soil related. So you're probably going to hear me speak a lot today about soil and fertilizer. I will fully admit I'm not a soil scientist, I'm not an agronomist. We fortunately have connections with great people who are those and now we're bringing something a little different to those fields with protein engineering.
Speaker 2:Cool. And last setup, before we go into phytases specifically, is what were some of the other projects right? So we talked about that really cool bio yeast detecting and then releasing a therapeutic. I think we talked about blood thinners In your lab. What are some of the other proteins you've engineered?
Speaker 1:Also during my PhD and postdoc we looked at other GPCRs. So one GPCR is the same one that humans use to see, so it's called rhodopsin. It's typically taught in undergrad about a prototypical cell surface receptor because it's immediately relatable why an organism would need to experience light and develop a brain signal in response to that. So we during my PhD we expressed those in yeast as well and studied how mutations that have been identified in people with inherited blindness can also make yeast be unable to see, and then can we rescue those mutations by a drug treatment. And that was actually my first experience with lab automation was a high throughput screen for screening for compounds that rescue misfolded proteins that cause inherited blindness. But it was again a very synthetic biology flavor project. It's creating yeast that can see, which is pretty insane, and then unfortunately making blind yeast so that we could then rescue with a drug using a robot. It was pretty out there. It was really cool. I really think it's a great project, but it was, yeah, really out there.
Speaker 2:Oh, that's so cool. I mean I'm throttling myself not to spend our whole time talking about that.
Speaker 1:Let's talk about yeast. Yeah, back to phytases, sorry.
Speaker 2:We have given yeast the ability to see and then for a lab project we took that gift away.
Speaker 1:Yeah, essentially, I don't know if there's going to be a bioethicist listening to that, but I'd love to get their opinion. Honestly, it was very strange.
Speaker 2:I absolutely love it. I think one of the big spirits that I think both in BioCanada and Homeworld Collective push is just like an ambition right and a thinking big in biology and I think sometimes we get held back by need to get one more validation, need to get one more control, need to think very small to get this one little grant, and so like when you hear stuff that's just at the frontier and I think not only at the frontier but well-designed, it's very cool. So I am glad that we touched on that. So let's talk about the big problem of phytases.
Speaker 2:And I, to be honest, I came across this because we did the garden grants and because we had, you know, we let, we really opened it up to people, saying convince us of a big problem and then how you want to solve it. And I remember that when we saw this, hey, there's this phosphorus in the soil and it's locked up, and everyone on the review team was like what? So I think it's just a really well-framed, beautiful problem. So I'd love just to have you introduce the challenge what is the problem that you're trying to solve?
Speaker 1:Thanks, dan, and let me say as well, for someone who's getting into the ag and food space, it was a great way to approach a protein engineering project. So anyway, I've learned a lot as well. The problem is, plants need essentially at least three main types of fertilizer, and you've heard of NPKS. So that's nitrogen, phosphorus, potassium and sulfur. Those are the main fertilizers that every farmer around the world needs. Phosphorus is very unique in that all life requires it, all life needs and PKS anyway, but all life uses it and it's also essentially non-renewable.
Speaker 1:There is no phosphate or phosphorus cycle, unlike nitrogen, which gets fixed from the atmosphere, or phosphorus cycle. Unlike nitrogen, which gets fixed from the atmosphere, phosphorus gets locked in rocks and it takes about 10,000 years for that to weather and then get back, released in a way that life can access it. So what that means is once phosphorus is applied to a field and once it runs off and enters the freshwater supply, you don't recover it, at least not in any kind of human terms. Right Like maybe algae are certainly using it. It's creating algae blooms when phosphorus runs off of fields and I, you know, witnessed those myself growing up in Ontario. It's surrounded by all these beautiful lakes, and particularly the Great Lakes and Lake Erie. You can see those algae blooms from space, and that's primarily as a result of phosphorus fertilizer running off of fields. So it's finite. It's creating algae blooms that disrupting our freshwater supply.
Speaker 1:But we need it and there doesn't seem to be a way of getting around applying it. So that was the problem. How do we sustainably apply phosphorus, and is there a better way instead of digging it up out of the ground? There is a hundred kilometer long conveyor belt that you can see from space. That is simply built to transport phosphate-containing rock from the middle of the Sahara Desert to the Atlantic Ocean and that is then distributed around the world. So there is a huge supply of this rock. It doesn't look like we're going to be running out anytime soon, but if there was a disruption to that supply in the middle of the Sahara Desert, we would have some serious problems around the world because of the finite necessity of phosphate fertilizer.
Speaker 2:And there's something special about that rock, where the phosphate is particularly easy for plants to liberate and metabolize.
Speaker 1:Essentially, yeah, it is refined in some way that I, frankly, don't know, but again, I'm not a soil scientist or a geologist but that rock is, it's a chemical source of this phosphate fertilizer, but there are also biological sources of phosphate, which brings us to phytase.
Speaker 2:And I think this starts with the intuition that I didn't know that phosphorus is a non-cyclical thing, but I do know that there's natural ecosystems and plants, and so there's must be phosphorus somewhere. So take us to the solution to this problem.
Speaker 1:Okay, so what I've mostly been talking about is inorganic phosphorus, and that's what is typically applied as the phosphate fertilizer. There is also organic phosphorus, which occurs in manure, and the primary source and it comprises about 50 to 80% of organic phosphorus is a molecule called phytate, and it is a very simple looking molecule, simply a carbon ring with six phosphate groups on it, and the primary source of where this comes from is actually from plants. Plants are producing this compound as a storage for phosphorus and also as a chelator for trace minerals. So, if you have a chemistry background or if you're able to picture it in your head, imagine a ring that is very negatively charged, so it's pulling all of these positively charged atoms into its sort of orbit and binding to them, and those positively charged atoms include iron, calcium, zinc, magnesium. These are all trace minerals that plants need as well, and they also occur in the soil, and that's the catch.
Speaker 1:So there's lots of this molecule that's produced by plants. There's lots of it in manure, but what happens in the soil is at the molecular level. This molecule is getting sucked up by these minerals and it's forming very tight bonds between these metal ions, and so it essentially becomes biologically unavailable and is locked in the soil unless a clever organism comes around and does one of two things, and that would be to release organic acids to change the pH such that it releases phytate from that kind of metal cage, or it uses an enzyme called phytase to cleave off some of those phosphate groups and so that it loses some of those charges and becomes more soluble, and then that phosphate also becomes bioavailable to those organisms.
Speaker 2:And so what do we know about phytases today?
Speaker 1:Yeah, so that's where we started actually around. When we applied to this project was when I decided I'm going to apply for a grant, but I'm also going to write a review paper so that I understand more about these proteins. And, by the way, for any junior PI, for anyone who has time to write a small review paper while you're also applying for a grant, is actually a fantastic way to learn about something and then go back to that same review paper to understand why you applied to that grant in the first place, so you can remind yourself about how these proteins work, because there's a lot of proteins out there and if you're going to engineer them, you got to know a little bit about how they work, obviously, yeah, so there's four types of phytases, basically, the means that nature has evolved four different solutions to the same problem, which is very interesting as a protein scientist. It also tells us that this problem is very important to solve from a biological point of view.
Speaker 1:Bacteria, fungi and plants produce these enzymes. Some work at acidic pHs, some work at alkaline, so higher pHs in the presence of metal ions, which is great. Others work in the middle, but they have very weak activity. Those are typically the ones that plants produce. So plants also are. Obviously, if they're producing phytate, they need a way to release phytophosphate from those molecules. But they more or less all have the same function, which is to release these phosphate groups from that carbon ring.
Speaker 2:And is the right way to think about it that the soil has kind of a phosphorus exchange going on inside the soil.
Speaker 1:Definitely, yeah, yeah, sorry to interrupt, but yeah, that is actually an interesting measurement that soil scientists use. They essentially look for phosphatase activity in soil to measure the health of that soil, so it's a proxy for the microorganisms that are releasing either phytases or organic acids. And how bioavailable then is that phosphate in the soil?
Speaker 2:Yeah, so big picture. The majority of phosphorus in a soil is organic phosphorus locked in phytate, and the objective is that we need to be able to. If we can unlock that from the soil, then maybe we don't have to ship from the Sahara desert, and so I think there's two questions here and I'm looking forward to explore. One is that I feel pretty humble when I talk about biology.
Speaker 2:I didn't pick up a pipette until age 30, right, so I have these constant moments of I know stuff and then I don't know anything. But if there's one thing I've learned is that oftentimes nature finds a way to really quote Jurassic Park, life finds a way. I'm really curious just to get this intuition of if this was so important. Why is this not being done better in nature? I'd love to just explore that and then also explore why are phytases hard to work with? It sounds good, it sounds important. Is it just? Is it one or two? Is this a one or two mutation away, or is it a bigger problem? Probably it'd be worth just to start with the Jurassic Park question, which is that why can't life just find a?
Speaker 1:way. It's a great question and I've pondered that as well. In fact, my lab mates have challenged me. They're like why don't we just pick a natural phytase? Why are we engineering these? And it's a great question.
Speaker 1:The simplest way that I can envision it is that life did not evolve to support modern agriculture. So there's lots of microbes in the soil that are producing phytases. We know that. But they're doing that for the benefit of themselves and they might have some type of symbiotic relationship with the plants around them. There's definitely microbes that do that and they signal with the plants and grow in harmony with them, but not at the scale that we need to grow food in the world.
Speaker 1:So there is no microbe that has evolved to our knowledge right to benefit directly modern agriculture, to benefit directly modern agriculture. So that's, I think, why we need to look at okay, we can take inspiration from these proteins and these microbes, but can we develop a product out of them? Instead of relying on what nature has tried, there must be a better way to enhance and this gets more into the meat of the science we're doing enhance the stability. So can we apply this enzyme as a product, for example, as we would a fertilizer and expect it to work over days, weeks, months, continually releasing phosphate in the soil, or a timed release perhaps, but at least lasting that long. And from a microbes point of view, they probably don't want to do that because they're releasing phosphate for themselves and that's enough, and then they can then divide. But if we want to release phosphate and use that as a replacement for the amount of phosphate that we apply to fields, it needs to be long lasting, needs to be robust, it needs to be timed and it needs to be highly active, and there's no natural solution to that. There's also the fact that, ideally, most soil that we farm is about a neutral pH, plus or minus one. So we're thinking pH six to eight.
Speaker 1:Most of these phytases that have activity are in a range that we can start to think of them being a useful fertilizer additive or replacement. They all work in an acidic pH. This is likely again because of these organic acids that are being released in that micro environment where those enzymes also are. But that isn't how a phosphate fertilizer would work. It doesn't deal in a micro environment, it deals with applying it to a whole field and expecting function across that whole field. So there's a catch there.
Speaker 1:We also need to think about what temperature they work at. Most of these are like a lot of enzymes. They have a max function around 37 plus and there's obvious biochemical reasons why that's the case. When you think about entropy so it's warmer, so the reaction happens faster. About entropy so it's warmer, so the reaction happens faster. But all of our agriculture is obviously in environments that are a lot cooler than 37 degrees celsius. So we need to think about soil and I was before just this call like. I live in canada and there's a blizzard right now, beginning of april, which is not much fun, but honestly, not too rare farmers are going to be planting in the next few weeks here. If they were expecting to use an enzyme that you would need at even like 25 degree Celsius or 30 degree Celsius maximum not going to happen in spring in Canada so we need to think about tuning that temperature down. There's no natural phytase that has been discovered that can do this.
Speaker 2:So the two questions there is one have we comprehensively searched for it? My hunch is yes, but it's worth just touching on because that's probably a natural question that a listener would have is that gosh once again? Has life already figured out a way? But then just assuming that answer is probably no. How are you engineering this? Because I'm really interested in how you're keeping the deployment in mind as you're doing some pretty complex protein engineering. But the first thing is do you think there's more metagenomic searching that we need to do?
Speaker 1:Definitely we're just scratching the surface, and even when it comes to sequencing we've come a long way. But then how do you pull out useful information from all of that data? That's not easy to do either. Yeah, so definitely there could be a natural solution as far as natural, like an existing protein that could function, like this maybe, sure, and that'd be great. I'm not going to say that's a bad strategy at all but, interestingly, for two reasons, that hasn't been the typical strategy for this problem. One is the strategy is to actually take a microbe that does produce a phytase and use that microbe as an inoculant in the soil, and that's already a product you can buy that now. It's a natural organism that has not been engineered, but a few companies that will sell you that they're not well characterized. Some they've done proper microbiology on, but some are mixed consortia. And again, not saying that's a bad idea, but I do think that if we want to tailor our solution and understand exactly what it can be applied for and when and where, we should have some sort of levers on that. That's where engineering can come in.
Speaker 1:And then the other aspect is that phytases are actually already a commercial product, but for animal feed, all of the phytases on the market at the moment are being used to treat grain for animals with less complex guts. So because they have less complex guts and that specifically means poultry and fish they're not able to digest the phosphate and phytate quite as well. So the phytate that's locked in these grains that chickens are fed and fish is actually anti-nutritive. It's sucking up all of those trace minerals as it's passing through the gut. So you want to treat, so you can buy this, and again it's a product. But think about the conditions of the gut versus the condition of soil. Right, a condition of the gut is acidic and it's warm. Soil is neutral and cold. So none of the phytases that are on the market are fit for purpose, but they've at least given us, I'd say, an in.
Speaker 2:Yeah, I have to just riff that to go back to the kind of like the inspirational syn bio. I think making a yeast sea is very beautiful and making a fish eat a burger is very uninteresting, but I get. So I understand now the motivation of why phytases are being engineered today, and I actually I do that there's it's somewhat counterintuitive from the outside looking in right that okay, this is what phytases are used for. I wouldn't have thought about animal guts in this, but that makes sense. And so to now center on your work now on this. It sounds like the assumptions are that there's four classes of phytases that you guys have found that's in your review paper and with those you probably need to pick the target. And then I'd like that you've got this deployment in mind. What are you doing to engineer it? How do you know if it's working?
Speaker 1:You would think, in the decades of biochemistry, that there would be an easy way to measure phosphate. And that's really what we're interested in, because if you have an enzyme that's releasing phosphate from your target, you want to measure then how much abundance or how much phosphate is released, and that you'd think that would sell. Turns out it's not so. The main techniques that people are still using and this is across the board were developed in the 40s. It's really old school chemistry that people are still relying on and it does work, but it's extremely fickle as far as handling. You need strong acids, you need to be working in a fume hood, you get a colorimetric readout and that's kind of it. So it's very hard to do a time course. It's very hard to change any of those conditions.
Speaker 2:That's incredible Really, yeah. Does somebody just need to engineer a GCaMP? Instead of sensing calcium, it just senses phosphate. That's an amazing like if you have to do high acids to detect phosphate. Anyway, that's my mind is blown.
Speaker 1:Yeah, and I think it's again one of those things where we relied on the chemistry knowledge of people 80 years ago and moved on because it worked well enough. There are other solutions, though, those we've started to use in the lab, which are enzyme based, so, to your point, like a GCaMP or another type of phosphatase or phosphate harnessing enzyme, those work much more reliably in our hands and are actually you don't need to use them in a fume hood you can automate, which is a big part of our work, which I haven't really touched on, but that is a big part of the whole. Purpose of this project is to flesh out our automation pipeline and harness that as well. So, yes, now that we have that in our toolkit, it's been transformational. We're not relying on 80, 90 year old chemistry anymore.
Speaker 2:Gotcha. Okay, so you've developed the assay. Tell us, how are you engineering? We've mentioned robots, but why are robots even being brought up?
Speaker 1:Yeah, it's all about how quickly can we measure the function. If you are interested in just changing one residue in a protein, you don't need a robot. But if you're building hundreds or thousands and you want to test them across concentration changes, temperature changes, ph changes, and then do that in triplicate, you're already thinking about the scale of hundreds or thousands of reactions. And that's where the robot comes in. Once we've defined the protocol, defined the experiment, using manual methods, it's a relatively simple matter of telling a robot okay, just do that, but repetitively over a thousand plates or a thousand wells, and that's where those come in.
Speaker 2:Wow, and you can span all those dimensions.
Speaker 1:We're getting there.
Speaker 2:Wow, what does this look like in a lab?
Speaker 1:It's relatively small. It's maybe six feet by two feet, roughly as far as the total size of the machine and it has a couple interesting features because it can and this is a liquid handler for anyone who's a little bit more familiar with these robots so it essentially is an automated pipetter, but it also has a few temperature controlled positions so we can change if we're interested in looking at soil, like temperatures, we need something that's cooler than even perhaps room temperature. So it needs to be able to cool or even heat if we're interested in checking those higher temperatures. So it just moves those droplets of liquid around and then heats or cools them. It sounds boring, it looks really cool, but the ability to iterate on that very quickly, you can load it up with what you need and walk away is transformational.
Speaker 2:And probably a little less soul-sucking than having to do that all by hand. Where does this work now? Is it in process? Are you at the manuscript stage? It's very interesting.
Speaker 1:I think we could write up a manuscript. So we've measured the function of 24 natural phytases. So this was at least this was to just say okay, can we measure function, and can we do that through a few different means, and I'll talk about one other mean that I'm really excited about as well. But that's where we're at and then can we use what we've learned as far as which ones worked and which ones didn't. Can we then design phytases inspired by those that don't exist in nature and test completely new phytases that are learning from? Okay, those ones work and those ones don't. So take the ones that work as a template and dream up more sequences, more proteins from those.
Speaker 2:I would love to just hover on one bit, which was you're saying kind of the new to nature, phytases, because whenever you talk about automation, it's on the flip side of AI and seeing in other fields like robotics. Right, ai and automation have had a different kind of path of first robotics and AI. Now they're merging with biology. I think the first thing people think about with AI and biology was AlphaFold. Now we're seeing more and more automation, and so it's just a very kind of broad question. But you're a world expert in this how do you see the interface of AI and automation in the future of biology?
Speaker 1:I love that question because AI is very hot right now, but there's also a lot of really garbage AI and essentially it's as good as what you feed it.
Speaker 1:And if we feed it really good data that we're confident in and a lot of really good data, then I would trust what the AI model produces. That's where automation comes in. So I talked about scale. It's about generating that really good quality data and doing that iteratively with a defined process that you control as many variables as you can and generating as many data points as you can. So that's the connection.
Speaker 1:It's being able to generate really good quality data that feeds into an AI model that you trust and you can directly's the connection. It's being able to generate really good quality data that feeds into an AI model that you trust and you can directly see the connection back to the biology. I understand I'm not an AI expert, but I understand it's always going to be a little bit of a black box, but if you have really good confidence in the data that you're feeding it, you can start to peel back those layers you can understand. Well, this is why it then produces this prediction, because of the results that you fed it in the first place. So yeah, that's the connection.
Speaker 2:And are you able to start hallucinating new phytases using the platform you built?
Speaker 1:Yes, definitely, whether any of them work. I'll stay tuned, and that's where we're at right now is okay, we're able to generate these we have some idea of. We certainly know how to measure them. Well, and then it becomes a question of, okay, how far away from nature can we get and will those still work? And we know intuitively and there's lots of publications about this now, if you have a protein that you've designed, the best way to tell if it's going to work or not is how close to a natural sequence is it? And that means that we're really bad at protein design. That's where we're at.
Speaker 2:Circular logic to the max.
Speaker 1:If you change a protein a little bit, it's still going to work. If you change it a lot, it's not. But there's lots of other things about our predictions that you can predict the pH that works at the temperature, substrate preference. You can make predictions about all of that. And now we're at the point where okay, do those predictions hold up?
Speaker 2:Got it? I think that is a perfect pause point on this. I think any protein engineer will listen to that and think, wow, that's cool. I can't wait to read this paper when it comes out and to hear more about it. We're just going to wrap with a quick rapid fire questions that we wrap all the episodes with. So are you ready? Yes, All right. Question one what's a single book, paper, art piece or idea that blew your mind and shaped your development as a scientist?
Speaker 1:Hyperion by Dan Simmons, because not only is it a fantastic book and sci-fi, there is really cool examples of synthetic biology in it, some of which are sinister and I think are ethically a big ethical problem. Others are more just practical. The idea of having a whole field dedicated to growing a material that is like one kind of throwaway line. There's this field for essentially growing plastic is in that book.
Speaker 2:but yeah, fantastic book it's amazing how many people answer the sci-fi book to that yeah we're the first to say hyperion. I love that book. Best advice line that a mentor gave you oh, I have two.
Speaker 1:One, it's very simple just say no. My old master supervisor, he had a post-it note on his computer monitor and just said just say no. And it's so easy to say yes because, especially in science, you're always so excited about learning and helping. I think is also something that a lot of scientists have, that need to involve themselves and help. But it's also okay to just say no and to draw those lines.
Speaker 2:I'm glad you said yes today.
Speaker 1:Me too, dan. I mean, I love Homeworld. I was definitely going to say yes. The other bit of advice is that you are your own best advocate. Hopefully you grew up then you feel like there's a great support network behind you. But I remind myself of that as well, that no one else is looking out for you all of the time except for yourself. Some people are selfish, and that comes easily to them and you can push that too far, but I think it's okay to remind yourself of that.
Speaker 2:I think that's fantastic. Yeah, we talk a lot about empowerment here. I think that's a very good way of coaching empowerment. Third question out of four if you had a magic wand to get more attention or resources into one part of biology, what would it be?
Speaker 1:Climate. That's why I love Homeworld. There's such a natural alignment there and I think synthetic biology has struggled for a long time to come up with a narrative. And people hear about synthetic biology and they think it's fake or it's somehow scary. But everyone wants to solve the climate crisis. Everyone is looking for innovative solutions for that, and that's where we definitely need more attention.
Speaker 2:I'm glad people can't see me blushing. Then Fourth question what is a skill that you think bioscientists need to invest more time into developing?
Speaker 1:Oh, boy Storytelling. Maybe that sounds a little trite. I don't know if I did a good job today, but I do try to tell a story about the who, what, where, when and why, and not just data dump, because it's very easy to do that and it's hard to break out of that reflex. But understand, like telling a story is essentially is what is the problem, and teeing up that versus this is what I'm doing in the lab right now. It's the why is so important.
Speaker 2:I love it. Those are all wonderful answers and I've really enjoyed this conversation. Ben so, as we wrap up, how can people find you and is there anything you'd like to close with?
Speaker 1:Where can people find me? I'm on Blue Sky. I've got a pretty cool publication coming out that's actually science policy. So if people are interested in that, find that. Symbio Canada I've handed off the presidency to a great individual, but I'm still on the board, so I'm still leading that and I'm sometimes in Saskatoon and sometimes I'm in Toronto. So if you're ever in either city, let me know.
Speaker 2:Cool Ben, it's been an absolute pleasure. Thank you so much.
Speaker 1:Thanks Dan, this was great.
Speaker 2: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 to our producer, dave Clark, and operations lead, paul Himmelstein, for making these episodes happen. Catch you on the next one.