Oomycota and fungal biotech with Mitch Roth

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Oomycota and fungal biotech with Mitch Roth

Today we sit down with almost pro hockey player turned fungal laboratory scientist Mitch Roth. We chat about plant pathogens, DNA sequencing, genetic engineering, fungal biotech, Oomycota, and more.

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Alex 0:11 Welcome, welcome. You are listening to the mushroom revival podcast. This is your host Alex dore, and we are absolutely obsessed with bridging the gap between you are lovely, incredible, beautiful listeners and the wacky, mysterious world of fungi and mushrooms. We bring on guests and experts from all around the world to geek out with us, and go down a rabbit hole into the fantastic world of fungi. And today we have Mitch Roth tuning in from Ohio to talk to us about all things myco technology and genetic engineering and, and many more topics. So how you doing Mitch? Unknown Speaker 0:53 Good. Thanks for having me, Alex. Alex 0:54 Yeah, so for people who don't know who you are, you want to give a little intro on who you are and what you're up to? Speaker 2 1:02 Absolutely. My current role is as an assistant professor in the Department of Plant Pathology at Ohio State University, and I'm on the Wooster campus in Northeast Ohio. I earned my PhD in genetics and Plant Pathology, I had two majors from Michigan State University and 2019. So I consider myself a geneticist and a molecular biologist, because that's what I was trained in some of those tools, but I have a passion for agriculture, because I actually grew up on a family farm in a small town called Bad axe, Michigan, it's up in the thumb area. Yeah, so. Alex 1:45 And it's my understanding that you wanted to become a professional hockey player. And that didn't didn't turn out. And so now, you're studying plants fungi in Ooh, my coda. So how? How did that happen? Speaker 2 2:01 Yeah, so everyone's career path is a little different. I acknowledge that. Like, most young kids these days, I wanted to be a pro athlete, and hockey was my sport of choice. It still is. We're currently in the NHL Stanley Cup Finals right now. And it's exciting time to be a hockey fan. But unfortunately, my skating and stick handling skills, we're not going to get me to the pros. Although at one time, I did think that maybe my interest in sports in my hand eye coordination that I developed in sports would be merged really well with my emerging interests in biology. And so I originally wanted to merge these things and become a surgeon and go into medicine. Because I really did love biology. That's what really hooked me at first. But I quickly learned that it was truly biology that fascinated me and not medicine. So I turned back to my roots and decided, you know, agriculture is a great place to study genetics and molecular biology, because plants and microbes have DNA just like humans and animals do. So that's how I eventually wound my path to my current position as a mycologist, and geneticist and professor. Alex 3:19 And what is the Roth lab at Ohio State University? And what do you guys do? Speaker 2 3:24 It's still a little bit weird hearing that the rock lab stores in August of 2021, at Ohio State, and my role in the department is as a mycologist. So my role is to study fungal pathogens of plants. And that includes the old my seeds, pathogens of plants, so my seeds are filamentous, a lot like fungi are, but on the Great Tree of Life, they're actually very highly diverged away from fungi. They're not very closely related on a genetic level at all, even though they look fairly similar under a microscope. So we particularly study these fungi in our mind seeds to try and understand what tools that they are equipped with, in order to infect a plant and cause a disease. Just like humans and animals. Plants are also susceptible to diseases caused by fungi and on my seats, but also viruses and bacteria and microscopic roundworms called nematodes. So we study the pathogens, the the fungi and Omega seats to try and identify those tools. But we also study the plants to understand what makes them more susceptible to infection more prone to infection, or if we identify a resistant variety of a certain plant, we try and understand that resistance as well. So in particular, in the Roth lab, we're trying to use molecular approaches to really understand the genetics behind this interaction between plants and fungi, plants and oh my see Eat. So that involves a lot of gene cloning a lot of genetic transformations, some protein expressions and a lot of time on the microscope as well. Alex 5:11 And for people who are not super familiar with, you know, plant pathogens, specifically fungal in my seat, I just realized that the the famous Irish Potato Blight was caused by an my seat. That's right. I thought it was a fungus for the longest time. And I just realized it was part of my coda. So why do you know why Mikoto got kicked out of the fungal kingdom. Unknown Speaker 5:45 So kicked out is maybe not quite the right Alex 5:48 way to think about it, it's just slightly moved. Speaker 2 5:51 So as we studied these things, more and more, we started to recognize that there are differences and these differences are actually quite significant. You know, even though fungi Annamaya seeds grow very filamentous. And if you're looking at a petri dish, they always grow in a radial fashion from the inside out towards the outer part of a Petri dish. But there's a lot of differences. And those differences add up as well. And the real true discovery of how different they were, was in part due to the revolution of DNA sequencing, when you start looking at fungi and all my seats on a DNA level, they share very, very little DNA similarity suggesting that they last shared a common ancestor a very, very long time ago. So to generalize very broadly speaking, fungi were once studied alongside plants and considered to be a strange form of a plant. fungi are actually more closely related to animals than they are to plants. And oh, my seeds are the opposite. They're more closely related to plants than they are to fungi. So really very different. Alex 7:10 Wow. They, I mean, they look like, you know, a fungus for sure. So that's, that's super interesting. And so, apart from the pretty famous, you know, Irish potato blight, what other what are the biggest fungal or who might see plant pathogens around today? And what are their impacts? And what is the potential solution? Speaker 2 7:40 Yeah, so the two that I like to highlight the first one we've already talked about, Phytophthora infestans is probably the most well known, oh, my seat pathogen because it was responsible for the Irish potato famine. There's a few other Phytophthora species that people may have heard of Phytophthora. ramorum, is a tree pathogen Phytophthora. So J is a soybean pathogen. There's quite a few Phytophthora pathogens of plants that cause a lot of disease. And then the other one in the fungal world that I like to talk most about is Boatright is scenario because it's the one that most people are probably familiar with. If you've ever left fruit in your fridge for a few days too long, and it gets fuzzy and gray. That's the fungus called Bo traders scenario. And it is considered a pathogen of plants. But it's more of a post harvest pathogen of plants. But since it grows in our refrigerator occasionally, that's why most people are aware of it. There's many, many more fungal pathogens, and I could talk about a lot of them. It's funny, there's actually two papers that were published recently talking about the top 10 fungal pathogens of plants in the top 10, almighty pathogens of plants. And so if you do some quick Google searching, you can probably find those and read more about the top 10s. Anyway. But the second part of your question, I think, was about impact. This is this is always fun to talk about as well. So I teach a course and again, I'm fairly new at Ohio State. So I got to teach this material for the first time, just this past semester in the spring, and I was trying to articulate this and I finally found some data to back this up. I thought it was really neat. So a recent paper tried to highlight the top 10 global pests and pathogens. So this includes all sorts of yield losses caused by any insects or pathogens of the top major crops. So the top major crops according to them were wheat, rice, maize, sorghum, potato and soybean. So these are all crops people are likely aware of. And if you consider all of the top pests sand pathogens. fungi alone are responsible for 43% of all of the pests and pathogens. Wow. And if you lump all my seeds into that, so all fungi and Oh, my seeds are responsible for 50% of the top pests and pathogens of the top major crops. So there's a huge number to demonstrate that that 50% of the top pests and pathogens are fungi, or are my seats. Alex 10:32 So you got your hands full. Speaker 2 10:34 That's one thing we'd like to call job security, there's lots left to learn. Alex 10:39 And what has been, do you have a favorite, fungal or oomycete pathogen that you you'd like to study? Speaker 2 10:49 Yeah, so I have to say my favorite fungal pathogen is this species called fuse Areum vernacular for me. And that's in part because I did my PhD on this one particular fungus. So when you spend five years with something that's a long time you become very invested in it. But also, just taking a step back from the molecular details of the fungus that I'm fascinated by, it also happens to grow this very pretty blue color in culture. And in fact, before they gave it a formal Latin name, they just called it fuse, the fuse Areum, blue isolette, it's nice to have a blue color. So that's probably my favorite, but we work on a lot of others as well. Alex 11:38 And a big part of your work as well is, is working with genetically modifying plants to be resistant toward to these pathogens, is that right? Speaker 2 11:52 Yeah, that's a big part of it. And, and on the flip side, also doing genetic engineering, with the fungus itself, or the Oh, my seat itself to understand what the genes are doing while infecting a plant. Alex 12:07 And I know a lot of people, you know, are a little nervous around the term genetic engineering, especially with organisms, especially anything that they're consuming. And regardless of you know, or despite there not being any research of any negative human effects of them, it's still this unknown, right of well, what if you know, we're playing God, and who knows what might happen and one fear is creating. And this is kind of a fear with a lot of like, like creating superbugs, or, you know, in this case, a super pathogen, where you're kind of creating a scenario where these pathogens are evolving quicker than they normally would, because you're forcing their hand basically to adapt and overcome. And then they become way stronger than they normally would have if we didn't intervene. And so what are your thoughts on this has this? Do you think this is a reality or more science fiction? Speaker 2 13:16 I think I think it's very much rooted in reality, I think it these are all valid concerns that I think, in part have been addressed, but also need to be an ongoing, active area of research to continue to investigate these things and make sure right, when, when you're asking this question about adaptation, I like to I have these conversations quite a bit. And I like to steal a quote from Jurassic Park, right Life finds a way it's right. That's what they say before the dinosaurs take over the island. Right? So you know, adaptation is something that happens all the time, and plants are constantly adapting, so our microbes, with or without human intervention. And so I think it's, it's what we do as scientists is try and help that adaptation occur even faster, and in an in a more elegant way. And that can cause selection pressures for the pathogens to overcome that resistance even better, and, and it could could produce superbugs, if you want to use that term. But, you know, that's why we study these things to make sure that we understand those risks and we're deploying these genetically engineered organisms and plants in very tactful and strategic ways. Disease Management should never be done with one tool alone. Did the disease management integration is a very common strategy. And so that can include cultural practices, like managing water Managing the soil content, the clay content, the pH of the soils, it can involve some chemical approaches, either adding nutrients or other types of if you're trying to manage pests and pathogens, insecticides or herbicides or fungicides, but then genetic resistance is also one of those tools in that toolbox. So if we can engineer resistance and complement it with these other disease management strategies, then it significantly reduces the chance of microbes evolving and adapting to all of those different situations all at once. Alex 15:43 And what would you say are the main bottlenecks of doing this research? Speaker 2 15:50 So it's pretty challenging. Although there are some companies that have gotten very good at genetic transformations, particularly in plants. A lot of my work in the lab currently is focused on the fungal and Oh, my seat side of things. So we're constantly trying to identify a gene of interest that we're curious about want to learn more about. And so we try and target that gene for a knockout mutation is what we call it. So we try and just delete that gene from the genome altogether, and then study the mutant strain and see, is it any better at doing something? Is it any worse. And that's quite challenging to do in some fungi. One of the issues that we face often is trying to convert the fungal hyphae, these long filamentous strings of the fungus into individual what I call naked cells that are technically technically called protoplasts. And once you have protoplasts, any sort of DNA that you expose it to, is much more likely to get taken up by the fungus and incorporated into the genome to replace your gene of interest and finally give you that knockout mutant. So that can be quite challenging. Is this critical? Is fusion. Not progress. But it's Protoplast. Coupled with transformation. Alex 17:18 Got it? So here is a huge genetic. Sorry, go ahead. Yeah. Sorry. I think there's a slight lag. I hear genetic engineering with with fungi is is extremely difficult. Maybe a little bit easier. For more. I don't know how to classify it more like yeast like fungi and more difficult with I don't know the correct term. I want to say higher level fungi. I don't know if that's the correct term, but or like mushroom bearing fungi? Is that true that they're a little more difficult than, say, bacteria or plants? Speaker 2 18:02 Sure, it's, it's hard to generalize too much. But yeah, I mean, in general, yeasts are more commonly able to be transformed, and you can insert DNA or take DNA out. Some filamentous. fungi are also quite easy at being transformed. And some are quite difficult. And in fact, even within one species, there can be a lot of strain to strain variability. So the higher fungi that you mentioned, typically, that means the ASCO my seats and the Presidio my seats and the basidiomycetes are the commonly known mushroom forming fungi. And I don't personally work on the mushroom forming fungi all that much I know that might disappoint some of your listeners interested in mushroom revival. In fact, a lot of the pathogens of the plants that I work on and a lot of the plants that grow here in Ohio, they are asking my seat fungi. And so we study a lot of those fungi. And some are easy to transform, some, some are not. Alex 19:10 And has there been something that you've been working on that you're completely stumped on that you are hoping to figure out in the in the near future? Speaker 2 19:20 There is, yeah, one project I'm really passionate about is a disease called white mold in soybeans. So white mold is caused by this fungus. This fungus actually has a very broad host range, it can infect a lot more than just soybean. But in Ohio, we grow a lot of soybeans. And so white mold can cause a very significant problem on a lot of acres of soybean. And that can affect the economics of the whole state even so. There's a certain protein that the fungus expresses that I've identified that I think is playing a major role in its variants, and it's in its ability to infect soybeans. And I think I've under identified a gene in the plant as well in the soybean that specifically recognizes that. And it's this recognition that actually makes the plant susceptible. And so one of the things I'm trying to determine is whether or not removing a gene from the plant from the soybean could actually enhance resistance, in a sense, could less be more removing a gene giving it more resistance. So that's like thing that we are just in the infancy of this project, but it's pretty promising so far. And so that's something I really hope I can work on even more and publish on in the next couple of years. Alex 20:52 Like, almost like removing an Achilles heel, you know, like removing that weakness? Unknown Speaker 20:57 That's a great way to think about it. Alex 21:00 And is that the normal is, is there a normal approach on how to approach kind of pathogen resistance? Like, do you? Do you normally work from the plant side? And find the weakness and cut it out? Or is each each plant pathogen you have a different solution for? Speaker 2 21:26 Yeah, great question. So every pathogen is a little bit different, every plant is a little bit different. And, to go back to your analogy, like removing the Achilles heel, the opposite side of that same coin is is adding more armor to the plant. Right? So there's two schools of thought. One is qualitative resistance is what they call it. So qualitative meaning either is it resistant completely, or is it not. And in contrast, there's a second school of thought called quantitative resistance, where instead of being such a binary, outcome resistant or susceptible, its quantitative, there's a spectrum of, of some disease, low disease, high disease, or somewhere in the middle. And so both are active areas of research around the country, my lab is still fairly new. And so right now, we are focusing a lot on the qualitative, just, you know, one gene at a time trying to understand if we can completely abolish susceptibility or completely bolster resistance through one gene. But quantitative resistance is, is also very commonly researched. So I'm, Alex 22:44 I'm neither a plant person, or, you know, I know very little about plants, and I know very little about genetic engineering. So this question, I'm going to try as hard as I can, but it might sound a little naive, but when so when you go to genetically engineer a plant? If you I'm guessing, is the normal process for? Is it taking clones? Or, you know, do you when you take the seed from the plants? Do they? Do they carry over those genes? Or do you every single kind of every, every single, you know, harvest season? Do you have to go in and and re reapply that genetic? Engineering? Does that make sense that question, Speaker 2 23:36 I'm gonna see where you're going. Yeah. So if if I generate a genetic mutant strain of either a fungus or plant in the lab, and I want to deploy it out into the world, first of all, you have to go through a whole bunch of testing from the US government to make sure that if you do that, it's not going to cause a devastation. So it's not easy to do. But let's say perfect scenario, I've studied something and I have this very resistant plant, and I want to release it into the world. If it's genetically engineered, most of the time that genetic engineering is heritable, so it will go from seed to seed. So if I give a farmer a genetically engineered seed, and they put it into the ground, and harvest it, all of the seeds that come from that plant will also carry the genetically engineered DNA. But there are some systems in place that prevent that heritability from happening. So you only get one generation at a time. I'm less familiar with that technology myself. And in fact, I'm not sure if that's even widespread in the plant community. I think these are things being explored a lot more in the insect world to manage insect control, like Mosquitoes through gene drives, which can propagate themselves through a population, but not necessarily be transmitted to the next generation. Alex 25:12 Interesting. Yeah, we brought on a researcher, Dr. Brian love it who was working in Burkina Faso in, in West Africa. And he was doing research on genetically modifying a fungus to kill an entomopathogenic fungi to kill malaria bearing mosquitoes. And the research was incredibly effective. It was like 99.9% effective, but he had to kind of abandon the project, because people were kind of freaking out about it. And they didn't want to let out a bunch of genetically modified mosquitoes everywhere, you know, with a zombie fungus attached to it. So yeah, and you know, it, that was kind of the the main pain point of the research was like, oh, you know, we couldn't, we couldn't convince people that, even though we proved, you know, in these in, you know, they made these like, I think they were called, like, bio reserves or something where they, you know, they tested it on mosquitoes, it was super effective. And, you know, and so, yeah, had to kind of abandon it. I don't know, if you you run into things like that with in terms of regulations, or just convincing people that this is okay, or is it pretty kind of green lights all the way through? Speaker 2 26:45 It's certainly not green lights all the way through. But my, my experience is also rather limited. You know, I think that is the ultimate goal for me, because I see the potential in the technologies. And a lot. You know, one of the things I'm also passionate about is talking about these things. And that's, that's one of the reasons I was really happy he reached out to talk to me through this podcast, because this is something I'm I'm interested in communicating about and trying to just teach people what I know, and also learn from other people, what are their concerns, and like you've said, there is a lot of concern about their about the genetic engineering and the potential unknowns. And I think there's two takeaways that I have there is that, first, it's really hard to prove a negative outcome will occur, you know, the lack of, of data suggesting that is, there's always going to be room for doubt, right? So it's really hard to prove a negative. And instead, all we can do is focus on the data, we do have suggesting that the technology is safe. And there's lots and lots of data suggesting that the things that have been released are very safe. So there should be little concern there. But then the other lesson is that there's there's always a chance, that's one of the the challenging parts about new technologies. And whenever I talk about these two things, particularly the last part, that there's always a chance of a negative outcome, I like to make the analogy to computers, right? Computers, at one point were a new technology and the internet was a revolutionary, new technology. And they have impacted our world in positive ways. They are facilitating this conversation between you and me right now. But there's also some bad uses of technology and malicious uses of technology, and some unintended, unintended consequences. I'm old enough to remember the y2k fear, right? Out of some oversight and an unintended consequence. So these are valid things to then apply to other fields. But one of the things that I hope by facilitating conversations between my work me and my work and others who are interested, is that I can demonstrate that we are working very hard to understand these things, the best we can and that that the technology has so much potential to have a positive impact that it's worth pursuing. Alex 29:30 Yeah, does does the positive outweigh the negative? And yeah, and it's, you know, it's important to always think about risk and how, how to manage risk. And I think with anything, there's always there's always going to be some risk, right? And like driving a car, like there's tons of accidents all the time. Some of them are fatal, but most of us if if we can if we live in a place where we're successful, getting a car every day. And we drive because it's convenient, and the convenience way out risk or outweighs the risk, right. And I always tell people, like, if they don't want to consume genetically modified organisms in their body, that's fine. But there's a lot of amazing things that I would love to cover with you that, you know, like micro remediation, for example, like if we can genetically modify a fungus to remediate 10 times more oil than it normally would. I mean, why not? You know, like, like, for that it's like, if we can tackle some of the biggest world problems and like, degrade toxic waste in our environment, like, hallelujah, you know, let's, let's do that. So, you know, 111 thing I was reading in your paper was that researchers were starting to engineer Saccharomyces service ca cells for production of fatty acid derived biofuels and chemicals. Woody, what do you think is the future around this? Speaker 2 31:17 Yeah, so I think the future is bright. And and I should highlight to that, you know, some of these awesome potential impacts of fungi. You mentioned, bio remediation. If we can genetically engineer that, that would be awesome. I agree. And some times that doesn't require genetic engineering, either. There's so much fungal diversity out there, that a lot of it we just don't understand, because we haven't studied the diversity deep enough and well enough to identify naturally occurring isolates that are capable of doing that. Unfortunately, mycology is a historically underfunded discipline. And so while genetic engineering can, I think facilitate these goals that we may have set for society to try and have a positive impact? You know, genetic engineering is just a tool. It doesn't have to be the only tool. But getting back to your Saccharomyces question is another great goal to shoot for, I think is engineering, yeast strains to produce biofuels is a little bit out of my field. I don't do a whole lot of that myself, but I'm interested in it. And I think one of the more positive impacts of that is that these biofuels are suitable for the current infrastructure that we have, the biofuel products can fuel our engines that already exist. So that alone is a big benefit, because they could continue fueling our current society while being sustainably produced through genetic engineering of yeasts. But I also think, you know, the sky's the limit, and who knows what other types of technologies we can identify through yeast fermentation, for instance, and all sorts of different byproducts that could be potentially converted into new fuel sources. So the future is bright there, but it is a bit out of my discipline. Alex 33:22 Totally. Yeah. You're and you focus a lot on DNA sequencing and genes. And DNA sequencing is not only to find new species, and to kind of classify who might CODA and in a different in a different kingdom, but also helping us identify genes. What what is the importance of discovering, you know, jeans, in new jeans in fungi, or Ooh, my seats or plants? Speaker 2 34:04 So gene discovery is exciting. I think if you get to discover anything, you get a sense of excitement. And gene discovery is still occurring in a lot of different organisms, including humans, animals, plants, and yeah, in particular fungi and Omega seats as well. So yeah, that's pretty exciting, pretty exciting, because you're never quite sure what you'll find. And if you do find one gene that seems to be very responsible for a given outcome. That makes for a very nice story to tell people and a great research project to pursue. But gene discovery can be you know, equally frustrating as it is exciting because fungi and all my seats are complex organisms, just like plants and animals. And a lot of times it's not just one gene that makes a difference. You know, one gene contributes to a small part of a pathway. And it's the overall pathway that produces the compound or the the trait that you're most interested in. So it's a double edged sword, but DNA sequencing certainly helps with the discovery of genes. And then it's the studying the role of those individual genes that can be either give you that eureka moment, or or make it very frustrating if it's part of a bigger process. Alex 35:34 And and genes, you know, for the layman, is there basically instructions to the organism? Is that right? Correct. Yeah, so the, Speaker 2 35:43 oh, I'm blanking on the, what they classically call it. The central dogma, that's what they call it, the central dogma of molecular biology is that DNA is transcribed into RNA, and that RNA is translated into a protein. And so the protein is what performs the function. And the DNA gives the instruction on how to form the protein. So yes, the thinking of it as a blueprint or a set of instructions is, is a good analogy. Alex 36:20 And like, what is the, the limits of this, right? Like? Like, could we could we use CRISPR, and another technology, whatever to, you know, genetically modify a fetus of a human to, and the code is basically like, grow another arm. And then, you know, as as it's being read, or whatever the right terminology is, you know, the baby grows another arm, because that was that was the gene that was the instruction. Am I oversimplifying it, Speaker 2 36:57 perhaps, but I think I get the gist. I mean, if if there were such a thing as an arm gene, and you were able to find a way to express that, in a certain stage of development, in a certain cell that doesn't normally express it, perhaps the end result might be a third arm, it's often not quite that simple. But occasionally it is. So in in the fungal world, there's lots of different chemistries, and chemicals that are toxic to a fungus. And so that can be really helpful in in a lab, where I'm trying to grow one particular fungus. And if another one comes in and contaminates my plates, I have to start the whole experiment over again. So fungicides can be very helpful in keeping things clean. But then also, we've identified how those fungicides work. And we can genetically engineer one or two mutations in the strain and actually confer fungicide resistance. And a lot of times, we use that as an initial marker to identify strains that we are certain some sort of engineering has taken place, because that's an easy trait to screen for. So if I have a gene that I'm interested in, that I have no clue what it does no clue at all, one of the things I might want to do is remove it. And instead of just removing it, what I'll also do is insert the fungicide resistance gene. And if now all of a sudden, my fungi are growing on plates with the fungicide. That means some sort of engineering has taken place. And I can now go in and confirm that the gene I was interested in is gone. And in its place is this resistance gene. And so now that's a certain strain. I want to study further because I know it doesn't have the gene I was originally interested in. Does that make sense? Alex 39:00 Yeah. Yeah. Interesting. Yeah. Yeah, keep going. Speaker 2 39:07 So when when certain outcomes or traits are controlled by a single gene, that can be very useful to help learn more about the organism. Alex 39:23 And another thing I was reading in one of your papers was the excitement over the advancement with I think it's pronounced Heisey. sequencing. Is that right? Yeah. HSC sequencing? Yes. So I was curious, what's the advantage of seeing a 3d model? Of of? I don't, what would you call it a 3d model of the genes? The genome? Speaker 2 39:52 genome? Yeah. So if you sequence all the DNA in an organism, you get what's called the genome. Now A lot of technologies that produce a genome actually fragment the DNA into many, many bits and pieces. And so we have to use computers to stitch all those pieces back together in order to make sense of it. And so the high C sequencing and developing a 3d model kit is particularly helpful when you're trying to separate out different genes or different alleles in the fungal genome. Because to, to bring it back to humans for just a minute, you know, humans, we inherit one copy of DNA from our mom, and one copy from our dad. So if we sequence our entire genome of us as an individual, and it gets fragmented all along the way, when you try and stitch those back together, it can be hard to determine if these three genes all came from mom, or if genes one and two came from mom, and the third came from dad. So creating that 3d model can really help you stitch together, which genes came from which set of chromosomes which set of DNA that came from which parent. So this is helpful for fungi for fungi as well, because some fungi live in a die carry otic state or a diploid state where they have two copies of everything. Some fungi live most of their life in a haploid state where they only have one copy. And so in those cases, we don't always need to use high C sequencing. And we don't always need to use a 3d model. But it's particularly helpful when when the fungi do have more than one copy. And some of the the most frequent culprits of this are the rust fungi. If you've ever heard of a rust pathogen, they infect a plant and produce these beautiful orange spores that looks like the plant is rusting like an old beat up pickup truck. They tend to be dichorionic and have two copies. And so high C sequencing has really revolutionized that particular area of research in the Rust fungi. Alex 42:18 And I'm trying to visualize this. So you know, a regular a regular genome sequence, you just get a long list of, you know, G C, T and A in random order, right? And it's just the list of letters. What what does the 3d model look like? Do you see kind of that that typical DNA spiral, helix shape or some other shape. Speaker 2 42:41 So it's, essentially the 3d model is still just stringing together the A's, T's, C's and G's, but it can do it in a very unique way that helps build confidence that, you know, the G and the C that you're looking at truly are right next to each other, rather than one G coming from one copy and the C coming from a different copy. And they're not actually related at all. It's it's quite calm, it's quite complex. And I understand just enough to be dangerous. Here's I mean, Justice To be frank, it's a newer technology, but the people who are doing this, they rave about it. We had a guest lecturer come to my class this past semester and talked all about it. And it was it was really fascinating how much it has revolutionized their study of the rest fungi. Alex 43:43 Cool. And in your paper as well, you're talking about how, you know we've demonstrated that both fungi and slime molds have decision making abilities and you know, how important it is to understand cell to cell communication and gene expression throughout the whole fungal network to see you know, what communication is taking place in say the hyphae versus or the hyphal tip versus you know, the main mycelial body versus the SType and whatever. How How is that understanding helpful for us for solving some of some of these world problems? Speaker 2 44:31 Yeah, so I'll be frank I'm not quite sure how it will help us solve human world problems but I think there's certainly room to explore there. And I think it's fascinating that you know, fungi and and slime molds and demonstrate this type of ability of making decisions or some sort of some sort of cognition perhaps in a form we don't fully understand. And maybe cognition and decision making are the proper terms, but there's something there. Right? I think my my thoughts on that are just, it's fascinating. And I think it's just an excellent example of how much we have left to learn from these other organisms that have been around for much longer than we have experiencing a lot more harsh and different environments than we currently experience. Yeah. And so it, we have a lot left to learn from them. And so the applications of that knowledge are bound to come, the more that we study them. Alex 45:40 So we've been focusing a lot on fungi and a little bit on plants. I don't know anything about my Kota, other than what you just told me. It's closely related to plants. And it was now I just found out like, an hour ago, it's responsible for the Irish potato famine. And then I read, I remember reading years ago that there's one that can infect fish, and lives in the ocean and makes these like weird brown spots on fish and get kill fish. And that's it. So what I guess my question is, are there are there solutions that we can partner with my coda to also solve some of the world problems like, like we are using with, you know, like phyto, or micro remediation or, you know, making biofuels or, you know, different medicines or things like that, like art? Are humans currently working with my Kota in a way to? That's helpful for us? Speaker 2 46:55 That's a great question. And my gut, my gut reaction is to say, no, no one is and that's because, again, my gut reactions say that, Oh, my seeds are pathogens. But that's a very narrow scope of things. There's a lot there's, there's a lot left to be learned from the Oh, my seat as well. You know, I mentioned earlier that that mycology is underfunded and under studied well. All mycology, the study of all my seats is even more underfunded and under studied. And a lot of the things that we do know about all my seats come from the study of all my seats as pathogens, either plants, pathogens, or fish pathogens. And so I think there's certainly room to explore them for their, their bio technical capacity and potential. But to my knowledge, there aren't very many people doing that. Alex 47:55 It's really wild, like I ever, ever, so often, I go and look at the biological tree of life. And I'm always blown away of how little I know, of everything on that biological tree of life. Like, I probably know, half, or I've heard, even heard of half of the things on that, that tree of life. And I'm like, there's so much we don't know, about the world around us. And it's fascinating, you know, about how much is still out there to to learn and to figure out what what's going on. Yeah, what is going on? Speaker 2 48:35 I want to reiterate that I'm not a taxonomist. And I'm not an evolutionary biologist, I, I am a more of a molecular biologist, I study one gene at a time, or sometimes a few genes at a time. I don't do a ton of whole genome things. And I don't explore many branches of the tree of life. But there are some really excellent researchers who do that sort of thing, and are constantly adding and updating that tree of life. And sometimes it comes at the cost of frustrating people like me, who follow one fungus is one name that has been called forever and ever. But, you know, the evolutionary biologists, you know, do enough sequencing and analysis to determine that even though it's it may be convenient to keep calling it that calling a fungus, that particular name. It's not actually accurate, and it needs to be reclassified if we want to keep things accurate and up to date. Alex 49:38 So it's like that joke. How many mycologists does it take to change a light bulb? And it's 41 to change the light bulb and 39 to stand around and argue about the Latin name. Yeah, yeah. So you know if you if you you already have a lab named after you the Roth lab at Ohio State University. But if you had an unlimited team and an unlimited funding and unlimited time, what research would you like to do? Specifically, you're on your own or in general, what research would you like to see done? Speaker 2 50:20 So, one of one of the joys of being a mycologist is, is working with yeast, and one of my favorite yeast based products is a cold beverage beer. So I think, you know, if I had unlimited funds and time and research, availability, I think it would be be so much fun to become a strictly yeasts, geneticist and engineer a bunch of different yeast strains, and do a bunch of fermentation experiments and be able to enjoy the fruits of those engineering efforts and engineer the perfect craft beer. Alex 50:59 Hell, yeah. Cheers. Cheers. Okay, sweet. And what's been what would you say is the hardest part of your, your research career? And it could, it could be, you know, one nightmare day or in general, something that you come across on like a day to day basis? Speaker 2 51:23 So, the related to the last question, the hardest part is getting funding, if I could get funding to become strictly a yeast geneticist, and do that kind of thing. I think I would jump on that in a heartbeat. But I'm not sure that job actually exists in the world, because it's, it's very hard to get funding to do that. And there's plenty of good beer out there with this the strains that exist in nature. So that has to be the hardest part is continuing to get funding to support the research, I think, you know, I try and make a pretty clear case of why it's important to do the research that I'm doing. And I try to tell the stories through research proposal that can articulate the impacts of the potential outcomes. But, you know, in grad school, we are trained a lot on how to do the technical research and analyze the results and write up the results. And not a little bit less on trying to present a pitch or a proposal that some sort of funding agency would be interested in supporting financially. So that's been the hardest part. And the second part of that is recruiting good people. I've been very fortunate to recruit some excellent people. But recruitment is definitely something they don't teach you in genetics class. So I've had to learn how a little bit on the fly on how to do interviews, and evaluate resumes and hire students and postdocs to do the actual research. While I'm in the office, coming up with the next great idea and writing the next grant. Alex 53:08 Nice, awesome, and what has been the most rewarding part of your, your time Speaker 2 53:16 The most rewarding part has been actually the people I have been able to bring in seeing them get as excited for a research project that I am, it's it's really fun to geek out over these ideas and, and experiments and have fun along the way. I think that's one of the things that I've taken some pride in is that, you know, research is going to be tough, but it should also be fun along the way. And so when I'm seeing the people I've hired, have fun and have success towards their research project. It's it's the most rewarding feeling for sure. Alex 53:56 Definitely. And if people want to follow your work and the work of of your lab and everything they're doing Where Where can they follow along? Speaker 2 54:08 Yeah, so I'm easily findable. If you just do a quick Google search you know, my lab page can be found on the Department of Plant Pathology website at Ohio State University. I'm also on Twitter my handle is Ohio my seat you know so encompassing the fungi and oh my seeds of Ohio. Alex 54:31 Yeah. Awesome. Well, thank you for coming on. And I really appreciate it I'm excited about what what is what is to come in and genetic engineering and understanding the genome of fungi and my quota and and plants and all the fun fun things with with the with technology and biotechnology and how we can solve Are our big, big human created problems that we have on our planet right now. So and thank you everyone for tuning in and tuning in to another episode wherever you are tuning in from from around the world. If you like the show and you want to support, we don't have a Patreon are anything but we do have a website, mushroom revival.com. And we have a whole line of functional mushroom products from gummies, to capsules, tinctures, to powders, and we have a bunch of educational resources there for free as well from blog posts, all our podcasts are there, we have a bunch of free ebooks that you can download. And if you want to win some free mushroom goodies, we have a giveaway going on. And it's the link is in the bio. And if you win, you get your choice of one of our products on our website, including my new book that just came out the little book of mushrooms all about 75 different mushrooms, which is super fun. And apart from that just tell your friends tell your family leave a review. Keep the mycelial network alive by getting people excited about biology and nature and mushrooms and fungi. So we can all live a more connected world. So thanks again everyone for tuning in. Much love and may this force be with you Transcribed by https://otter.ai
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