The future of lipids in evolution
Microbes are awesome, says biologist Paula Welander.
They have shaped Earth’s chemistry and its environment over billions of years, including oxygenating the planet to make it habitable for larger life forms. In turn, microbes have been shaped by that very same environment, evolving as the climate has evolved, she says. Welander now studies the lipid membranes of ancient microbes, which can endure for millions of years, to understand this evolution and where we might be headed in the future. Microbes are our connection to the ancient world, Welander tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. I thought it would be good to revisit the original intent of this show. In 2017, when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics. Stanford University and all universities, for the most part have a long history of doing important work that impacts the world. And it's a joy to share with you how this work is motivated by humans who are working hard to create a better future for everybody. In that spirit, I hope you will walk away from every episode with a deeper understanding of the work that's in progress here, and that you'll share it with your friends, family, neighbors, coworkers as well.
[00:00:48] Paula Welander: So, this planet has been in existence for 4 billion years, and you have to imagine that the first 3 billion years of the planet, and life evolved very much soon after the planet formed, those first 3 billion years is all microbial. So, we really don't start to see more complex organisms until the later part. And you know, humans haven't been around on this planet that long compared to microbes. And so, for geochemists that are really interested in thinking about what the Earth was way in the past and how it interacted with life, they need to understand microbial life.
[00:01:26] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. If you're enjoying the show or if it's helped you in any way, please consider rating and reviewing it on whatever podcast app you use. We love to get a 5.0 if we deserve it, plus your comments. Your input is extremely valuable to help others discover The Future of Everything. Today, Paula Welander will tell us that the lipid molecules or fat molecules that make up the membranes that surround cells are incredibly complex and they can last for millions of years. Long after an organism dies, that allows us to study the evolution of chemistry on Earth and the evolution of life on Earth. It's the future of lipids on Earth. Today we are continuing our new feature that we're calling the Future In a Minute at the end of the interview, I'll ask Paula a few rapid-fire questions and she'll give me some quick answers.
[00:02:25] Lipids are fat molecules that have many functions in the cell, but the most important is to create the membrane or the barrier that surrounds a cell. That's what keeps the inside of the cell separate from the outside. Now, not all cell membranes are the same, and across organisms we see different membranes with different physical properties because of the different environments that the cells live in. The cells in our liver and the cells in our brain have different environments, but especially single cell bacteria that are living in a hot springs in Yellowstone Park or in a very acid bath part of the ocean. They need very special membranes, and in fact, there is a huge diversity of the lipids that make up the membranes of these organisms.
[00:03:11] Not only that, but it turns out that the lipids can last almost like fossils for a long time, millions of years. You can take a sample, and you can identify the lipids and using your knowledge of what kind of lipids go with what kind of organism, you can kind of create a tree of life over millions of years to see what organisms were living where and why. That also helps you understand the effects of these organisms on Earth itself as they helped model the planet over the 4 billion years that's existed. Well, Paula Welander is a professor of Earth science and an expert on lipid biochemistry. She's looking at how lipids differ across different bacteria, especially, and a new branch of life called Archaea. And she's also looking at how those differences might lead to differences in how Earth has evolved and also what are the effects on humans.
[00:04:06] Paula, to start out, why do you study the lipids or fats used by bacteria and other organisms on Earth?
[00:04:13] Paula Welander: So, lipids are kind of, I think, I would say the unappreciated macromolecules of life that we have. I think we think they're kind of boring. They kind of just form, you learn from high school biology, kind of the membrane of a cell. But, you know, if we think about all the other macromolecules, there's DNA, there's protein, there's RNA, um, but lipids can also be dynamic. Um, they can have, um, particularly when you look in the microbial world, you start to see these differences that are very unique and interesting. And lipids are one of the few molecules that can actually be preserved in the rock record billions of years in the past. So, if you think about like DNA and protein that can be preserved, I think now we're saying DNA is like hundred thousands of years, which is amazing that you can get DNA that far back. But lipids can go even further back. And so, for many years they've been used as what we call molecular phos or um, biomarkers by geochemists who are interested in understanding life in the past. So aside from all the functions that we can study from them biologically, they have this connection to the ancient world. And so, I think that's kind of why they were exciting to study.
[00:05:19] Russ Altman: Yes, that, that does sound. So let, let's go back to some basics. You, you, you reviewed a little bit of high school biology, but since we don't wanna lose anybody, so the general idea is that these, um, when you, when you draw a picture of a cell you bought, you draw a big circle. And that circle is actually the, you know, the barrier between the outside world and the inside of the cell. And tell me if I'm getting this wrong. But that, that barrier is made out of these things called lipids. Uh, and I think what you just said is the lipids are, um, different across different species. Is that true?
[00:05:48] Paula Welander: Yeah. So, they can be different. So, the overall structure of a lipid, this idea that if you remember like from high school biology, you have like a hydrophobic inner core and a hydrophilic outer core, and they form this bilayer. That is kind of a, a basic principle of life, right? We need an encapsulation. And, um, but microbes are, especially their, their membranes are especially important because it's their barrier from their inside to the outside environment, 'cause they're single cell organisms. Now our cells are encased in our body and we have cells. All kinds of different cells. There's a barrier, many layers.
[00:06:21] Russ Altman: Right. There's like layers of protection.
[00:06:22] Paula Welander: Right. Yeah. But for bacteria and Archaea, these microbes, like they're in a, in a, in a lake, and they're, that's the environment they have, and they have to protect themselves from the environment. So many microbes inhabit environments that we consider extreme, like hot springs, um, acidic environments, alkaline environments, and they have to kind of modify their membrane so that they're able to resist a lot of the stresses they have out there. So, if you look at the, like I said, the basic principles the same, but if you start to look at the chemistry, that's where you start to see some diversity and some interesting kind of features that they have. So, our cells have pretty boring membranes. They don't really change 'em that much. Um, but microbes really, and what that leads to is not just this idea that different structures can be preserved differently. And so, you can see different microbes in the past based on their lipids, but also the biochemistry we can discover and uncover from how they form these lipids is unique.
[00:07:15] Russ Altman: Okay, great. So, the, now I want to go back. So, this idea, I mean, I, I get very excited whenever somebody says billions of years ago, and, and I think you said that, and so, uh, I, I, um, so, so you, so we, uh, you're, you're a professor of Earth science. So that, it was, it was very surprising or somebody could be very surprised to see, you know, she's a professor of Earth science, but she's studying bacteria and now she's using the words billions of years ago. So, paint a picture for like what was happening billions of years ago. I guess the Earth is about 4 billion years old if I'm, if I'm not mistaken. So, 4 billion years ago, obviously there was no humans. There was not even any dinosaurs. Probably there was just these single cell organisms, and they probably had to have these membranes that you're talking about, these, these lipids. So, can we, uh, actually learn about the Earth billions of years ago by this kind of study? And, and how does it work? Like how do you, how do you learn stuff?
[00:08:06] Paula Welander: Yeah. So, absolutely. So unfortunately, we can't go all the way back. We, we don't have records 4 billion years back, but that is the estimate of when life first emerged. And yes, the first forms of life were microbial. Um, so this planet has been in existence for 4 billion years and you have to imagine that the first 3 billion years of the planet, and life evolved very much soon after the planet formed. Um, those first 3 billion years is all microbial, so we really don't start to see more complex organisms until the later parts. And, you know, humans haven't been around on this one in that long compared to microbes.
[00:08:42] And so for geochemists that are really interested in thinking about, um, what the Earth was weighed in the past and how it interacted with life, they need to understand microbial life, right? They need to understand how do you connect, you know, modern day microbial life to the past? That's what geologists do. They're really great at, uh, going back to the rock record, which is our really our only historical record of our Earth's history as well as life's history. Um, so if you're interested in microbes, you know, 2 billion years ago, interested in the planet 2 billion years ago, what kind of fossils do you look for? Now, microbes don't, are not dinosaurs. They don't have bones, right? So, they don't leave,
[00:09:20] Russ Altman: Right. This was the surprising thing is I thought that there would be no way we would see what bacteria were hanging out. 'Cause they would be too squishy and just degrade.
[00:09:28] Paula Welander: And that's absolutely true. The majority of an organism, like a single celled organism in an environment that's over 2 billion years would be degraded. Because, you know, that process of like, you know, the sediments turning into rocks is really, really rough, right? It's hard.
[00:09:43] Russ Altman: It's pretty rough. Yes.
[00:09:44] Paula Welander: And so, the fact that they can find lipids is one of the most amazing discoveries that was made. And then the, the challenge is connecting it to what it means, right? So, you find this molecule and you're left with this, well, what is this molecule telling me? This, this chemical fossil. And, you know, how do we know that like a dinosaur bone that's found in the, in the, you know, geological rock record is like, like a leg bone is because studying anatomy of animals today you understand that. So, what we do is we study microbes today and how they make these lipids to help the geochemists understand what the connection is to the past, right?
[00:10:19] And so a lot of times they just wanna know who makes this. A lot of what we call these molecular fossils can be orphaned. They find the fossil, they find they find an organism. And so, we are able to kind of harness genomic approaches to kind of identify organisms that might have these lipids. And then once we find that we can do a lot of studies in the lab to understand, you know, is this just a membrane lipid or does it go beyond that? Are there certain conditions in which the organism will make this lipid. For example, it gets really hot, you know? Okay. Well then is that saying this environment, this geochemist found the lipid is a hot spring? Or is it one kind of connection like that to the environment?
[00:10:55] Russ Altman: So, this goes back to what you were saying about they have to adapt, especially the single cell organisms, because they could be in a very hot spring, they could be in acid. And so that's gonna manifest as different choices that they make so, choice so to speak, about how to build up their, their, um, outer membrane. And if you, and is it the case that some molecules that you find indicate that this was probably an acid living bacteria and other molecules tell you something else about its lifestyle, so to speak?
[00:11:22] Paula Welander: Yeah, exactly. Some of the lipids that, we don't study these lipids, but some of the most interesting ones are, um, um, the, um, the pigments that are found in photosynthetic bacteria. So, it can tell you, like it, you know, different pigments absorb light at different depths, so it can tell you about kind of how say an ancient ocean was stratified and how deep the light would go if you can see these different kinds of lipids at different layers. So, it can give you that kind of granular information. And so, you might ask, so who cares? Who cares if there were microbes in the past? Why do I wanna know? Well, microbes have impacted our planet's chemistry for billions of years. Earth did not look like it did today from a, like a physical standpoint, um, like it did 4 billion years ago.
[00:12:02] It's completely different. There was no oxygen. As a matter of fact, it was bacteria that invented oxygenic photosynthesis that oxygenated the planet and allowed all of us to evolve, you know, animals to emerge. Um, so this is why we want to understand that kind of connection, that interplay between how life evolved, particularly microbial life, and how the chemistry and the geology of the Earth evolved and how those two things pulled on each other, right? Because as the Earth is changing, microbial life changes, and as microbial life changes, then the Earth changes. And that's this kind of coevolution of life and Earth that we're really interested in.
[00:12:36] Russ Altman: And it is amazing to think that the amount of bacteria on Earth was and is so big enough so that it could actually change things like what the atmosphere looks like and, and, and of course, I'm sure it was breaking down the rocks in some way. Okay. Well, I wanna get, so you, you mentioned these, we've talked about billions of years, and we've made a little bit of a, a nod towards kind of evolutionary changes. And I know that there's a branch of life that you're especially interested in, uh, and, and, and, and is one of the topics that a lot of your recent papers have focused on. So, tell me about, uh, how you look at the Tree of Life on Earth and what is this special branch that, um, kind of is underappreciated?
[00:13:14] Paula Welander: Yeah. So, when we think about life, for a long time, life was divided into like roughly two kinds of, of organisms. We called them prokaryote and eukaryotes. And the only difference between these organisms was that eukaryotes, like you and me, have nucleuses in our cells and bacteria. Prokaryotes do not. So, within the bacteria though, like there are single celled organisms that we thought were bacteria when we looked at their genes, turned out to be a completely different group of organisms evolutionarily, right? So, if you look at 'em on the microscope, they look like a bacteria. But when you actually do the, what we call molecular phylogenetic analysis to look at their genes and see how they're related evolutionary, it was this group that's no more closely related to any bacterium than it is to us.
[00:13:55] Like they're kind of like their own little entity. These are the Archaea. These were discovered like in the 1970s. And since we've been studying the Archaea, we have found them that they are present all over the planet. And we usually find them by sequence. We actually, they're hard to culture sometimes, um, and they have interesting molecular biology and one of the things I'm excited about is their lipid membranes completely different. And so, they're very old. There're as old as the bacteria. So, you have to imagine like the first cell emerges, the origins of life, and then very quickly split into these two groups, the bacteria and the Archaea.
[00:14:28] Russ Altman: And this is way before the eukaryotes, way before the, the, the nucleuses.
[00:14:32] Paula Welander: Yeah. So, this is like, we're at about 3.8 billion years ago. We're estimating.
[00:14:36] Russ Altman: Wow. Three point. So, Earth is only a couple, a hundred million years. And already we're seeing signs of life.
[00:14:41] Paula Welander: Yes. Yeah, absolutely. And then, so you have these two, and when you look at the membranes, like the chemistry of the Archaea, they have a completely different like hydrocarbon chain and the way they fuse their membranes together to make the hydrophobic and the hydrophilic is different. For many years, the majority of Archaea that we were able to culture were from very extreme environments. Like they grow at like a hundred degrees Celsius. I dunno what that is Fahrenheit. Boiling, right? Acidic environment.
[00:15:09] Russ Altman: It's very close to boiling, if I'm not mistaken.
[00:15:11] Paula Welander: You know, very acidic environments. And they've modified the chemistry converted like ester bonds to ether bonds, which are more resistant and you can't break them as easily.
[00:15:20] Russ Altman: Ah, so that's part of that signature that you said we would see of strengthening based on the niche that they're living in.
[00:15:26] Paula Welander: Exactly. And so, as we've come to appreciate the Archaea, we've noticed these differences. And so, for me, uh, loving lipids, that's what I, I wanted to study. And although we knew how bacteria, now, our lipids are just like the bacterial ones, right? And so, the big kind of like, um,
[00:15:43] Russ Altman: Oh, really? So, we are closer to bacteria in our lipids than we are to these Archaea. Oh, that's interesting.
[00:15:49] Paula Welander: In lipids. But it's funny because in recent years as our genomic sequencing has gotten better and better and our, like, our evolutionary analysis of genes across all domains of life. So, across the bacteria, the Archaea, and everything else, the eukaryotes, turns out that our ancestor were probably descended from an Archaea. So now you have the, you know, and there's a lot of features of the Archaea in terms of like cell division and how they transcribe their DNA. That is more, more, uh, reminiscent of what we see from a molecular standpoint in eukaryotes. So, they're kind of like this,
[00:16:23] Russ Altman: So now we're getting serious. 'Cause these are our, not our just our relatives, but they're our ancestors.
[00:16:28] Paula Welander: We think they're our ancestors. And so, in my, in my lipid world, there's this thing called the lipid divide because you think bacteria and Archaea split. And then from the Archaea come us. But our membranes look like the bacteria. And so, how did we switch our membranes completely to resemble something else? And then why? Is it because we don't live in a hot spring? I dunno. But how that happened is such a black box. We know it happens because the, the data right now really does say that we descended from a group of Archaea. It really does say that that's where we're coming from. There's still some controversy in that. Some people don't totally buy it. But if that's true, then there's a real difference in terms of our membrane structure, the chemistry.
[00:17:12] Russ Altman: So it seems to me, uh, it seems to me that, uh, we, we split from the bacteria and at that time when we and Archaea were basically the same, either the Archaea changed from away from bacteria, but we stayed, or we were more like Archaea and for some reason we went back to being more like bacteria. I'm sure that that's what you're trying to figure out, right?
[00:17:32] Paula Welander: Yeah. And, and you know, how do you figure that out? It's kind of, it's really hard question to answer. I don't, a lot of evolutionary questions we're never gonna be able to. But one of the things you need to do is you just need to understand the basics, you know, of the chemistry, right? And so, in the Archaea world, there just hasn't been a lot of work done on the basics of what their lipids look. Now, the, in particular, the, the Archaea that we are thought to be descendant of, those have been really hard to bring into the lab. We know they exist from genomic sequencing because sequencing has gotten so robust. You can just sequence dirt.
[00:18:04] Russ Altman: So, these didn't die out. These are still hanging around on Earth.
[00:18:07] Paula Welander: Well, probably our descendants died out, but, but yeah. But descendants of these, uh,
[00:18:11] Russ Altman: Something that's close to what might have been the ancestor.
[00:18:14] Paula Welander: They're there in their environment and, um, about, I think in 2020, the first one was isolated in culture. Um, and it took 10 years to culture it. And you can't culture it on its own. It has to have a partner, another bacterium in there. Um, and so there's a lot of like, uh, nuances about bringing these into the lab because that's what we like to do as microbiologists. We wanna see it. But two more have been cultured. This summer I went to a conference where they were actually doing cell biology on them. So, they looked at them under the microscope and they're, they're pretty weird looking. They're like round and have these appendages. Um, and so what I wanna know, and, and I don't think anyone has done that robustly, is what do the lipids look like? Because if this is our closest to descendant, do they have a membrane like the other Archaea, or is it different? Does it look more bacterial? That's what we don't know. And so, I think kind of understanding that will help us understand the, the steps to how things change. Because you pointed out two different scenarios we could have for how our membranes have changed over time.
[00:19:11] Russ Altman: Now, uh, now when you, uh, going back to the molecular fossils, uh, that when you find these lipids. Do, do they retain enough of their kind of original chemistry so that you can recognize unusual molecules? Or have they broken down so much that it's very iffy what they actually look like?
[00:19:28] Paula Welander: Yeah, it depends on the lipid. Um, but the ones that are the most, what we call robust biomarkers, have retained a lot of their information. And the reason the ones from the Archaea are really interesting is because they, they are, um, made to kind of resist kind of tough environments that they do preserve a little bit better, and the changes in them, the modifications that they make are preserved as well. And so, you can see these changes under, over time and you can make like kind of connections to the environmental conditions, but it does depend on the lipids. There's some lipids that don't preserve at all.
[00:20:01] Russ Altman: This is The Future of Everything with Russ Altman. We'll have more with Paula Welander next. Welcome back to The Future of Everything. I'm Russ Altman. I'm talking with Paula Welander from Stanford University. In the first segment, Paula told us about lipids, membranes. She told us about the bacteria and how they have different types of membranes based on their niche that they're living in, and that these can be used for archeology because the lipids can last for millions of years. It's an amazing story, and in this segment I asked Paula about sterols, cholesterol, one of our favorite lipids as humans. Not really. And what role it has, if any, in bacteria and Archaea. I'm also gonna ask her about Archaea in our gut. Are they there? And what do they do?
[00:20:58] Paula, I wanna start out asking you about, uh, sterols, which include cholesterol because I know they're an important, uh, component of human membranes and I was just wondering, do they play a role in any of this kind of lipid archeology that you're doing?
[00:21:11] Paula Welander: Yes. So, cholesterol and other sterols, um, that have that kind of similar structure, can actually, are some of the most well-preserved lipids. They go back about,
[00:21:20] Russ Altman: Wow. Well, so they do well in the, in the rock.
[00:21:22] Paula Welander: They do and they do. 'Cause they're like a bunch of rings. They're like four rings and those rings are really, um, um, hard to break. Um, and so for many years they were used as biomarkers for, um, um, eukaryotic organisms like algae. You know, single celled organisms, but you carry eukaryotic. And they've been used to trace kind of, uh, how are oceans shifted from being predominantly like bacterial dominated, um, to being shifted to being algal dominated, which our oceans are dominated now. And by following the sterol marker over time, you can make those connections. It's also, you can use them to kind of trace when sponges, which are the first animals that have ever evolved, when those kind of potentially evolved because they also make cholesterol like molecules. And so, that's where I came at it because I was looking at different biomarkers that needed to be studied. And one of the big questions for me as a microbiologist who loves bacteria and Archaea was like, well, do bacteria make cholesterol?
[00:22:15] Do they make sterol? And the answer was no. It was, this is something that's very restricted to eukaryotes and that's why it makes it a good biomarker, right? Because it's restricted. But I found this paper from like 1971 that said there was a couple of organisms, they did not produce cholesterol, 'cause cholesterol, you need like 11 biochemical steps to get to that final molecule. But it produced kind of a precursor to cholesterol, so it is a sterol. And so, then I thought, well, they, the geologists have known since the seventies that this makes sterols. Why do they say it's only eukaryotics? So, it turns out that only like five strains of bacteria in the world made sterols. The sterols they made were not cholesterol. They were what we call sample sterols. And so, geochemists ruled them out as a source. But I was like, I dunno. I just wanted, and I wanna understand why particularly like the subset of bacteria would produce the lipid. So, you know, aside from the.
[00:23:05] Russ Altman: Right, 'cause bacteria just don't do things randomly. They have a reason.
[00:23:09] Paula Welander: Right? And if they evolved it or if they acquired it from somewhere, if they, you know, stole it from somewhere.
[00:23:14] Russ Altman: It had some function, it something, so it was something that was useful for the bacteria in its niche.
[00:23:19] Paula Welander: And at the time when I started to go into this is when we started to explode in genomic sequencing. And we knew the genes required to make sterols, and so I just looked in genomes. I mean, at the now we have like 150,000 bacterial genomes. At the time when I did this, it was like a thousand. It was like, oh, that's so many. Um, but yeah, I found other bacteria that had these genes and so the quest became to be like do these organisms make sterols? They do. And then I had one student who was very interested in these weird microbes known as myxobacteria that are found mostly in soil. Um, and they kind of, uh, they grow like they form these like structures. They kind of look kind of weird in the microscope, but I was like, these are really weird. She's like, I think they make really complex sterols, and she found cholesterol being produced by one of these.
[00:24:02] Russ Altman: Oh. Oh, that's a big one. That's not just a sterol.
[00:24:04] Paula Welander: No. It's not just a sterol, it's a sterol that's associated with vertebrates, right? It's our sterol, right? We make cholesterol and so we make this joke about do these bacteria get heart disease?
[00:24:15] Russ Altman: Right, right. Exactly. Do we need to give them statins?
[00:24:17] Paula Welander: So, sterols, and I think, you know, cholesterol does have a bad rap like it causes, but it's an essential molecule for us, for any organism that makes it, um, they, they utilize it for complex multicellular organisms. It's important in development. If we don't move our cholesterol around in our cells, if we don't move it out of like our organelles into like the membrane, uh, that trafficking can cause diseases. There are diseases associated beyond, like high cholesterol, heart disease, um, that can occur if you're not utilizing cholesterol as it should be used, right? If it's misused. So, my question was then like, okay, so what about, what is the role of it in bacteria? Is it just to rigidify the membrane, which is the main function you see with cholesterol? So, when,
[00:25:02] Russ Altman: Even, even in, even in us. Even in humans, it's, it's making our membranes a little less bending.
[00:25:07] Paula Welander: Yeah. It's a, one of our responses. So, if we have a stress response, if our membranes get a little too hot or something, they will put a cholesterol in there to help rigidify it, right?
[00:25:16] Russ Altman: Oh, that's interesting.
[00:25:16] Paula Welander: And it helps reduce, uh, permeability. So, it's just a way to modify the membrane to produce this lipid that they're already using for other things. But the main function we always think is kind of rigidifying the membrane, but we know from lots of studies that there's other functions. So, my question was in bacteria, are there other functions? Um, and so we started at a very basic level, like in that organisms that make cholesterol, my student realized that it doesn't have the full cholesterol pathway to every protein that's required that you see in, in humans, right? And she found that like in the middle there's like these unique bacterial proteins that are doing some interesting biochemistry. So, not only did bacteria acquire cholesterol, but then they evolve their own proteins to be able to, um, make the molecule.
[00:25:57] So you have the same molecule made by different pathways and, you know, that's, you know, that's really interesting why they would do that. And, but to your point, they do it for a reason, right? Why are they gonna evolve these proteins to do that? Um, and so that's where we've gotten with this organism. Um, where my future work is going now is I'm really interested in understanding beyond just like how they make it, is why they make it, right? And studying, um, what other pathways it interacts with. I, you know, my suspicion is they could be helping in signaling and helping the cell develop in some way because these cells are a little more complex than most bacteria.
[00:26:31] Russ Altman: Yeah. I, I'm struck by this because you're, you're studying this bacteria, but, and, but you're gonna learn things that cholesterol does that we may not even know, and it may actually reflect back on human biology in, in unexpected ways. There's no promise that that will happen. But by doing a deep dive into the, the what's going on in the bacteria, it, you may say, oh my goodness, this could explain such and such in human systems. Well, in the last few minutes I wanted to get to the one other issue, which is, uh, your gut. Your, your, are we having Archaea in our gut? We all know that there's a ton of bacteria living in our intestine. And that it's good, it's good, this is not bad bacteria. They help us live. They, they're like, uh, commensal organisms that do something to help us. What about Archaea? When you look in the gut, do you see 'em?
[00:27:14] Paula Welander: We do see Archaea, um, and you see a very limited number of Archaea. This is actually a new area of research in Archaea biology kind of thinking about, um, how we interact with Archaea with humans. So, Archaea do not cause any disease. So, this is probably another reason they haven't been studied as much, but we do have surprise, surprise, methanogens in our gut and methanogens archaea. And methanogens are known for making methane gas.
[00:27:37] Russ Altman: Methane gas, and we all are familiar with that phenomenon.
[00:27:40] Paula Welander: Yeah, so about I think, I think the number is about 10% of the population have some kind of methanogen in their gut. Um, and they're trying, people that study this, um, they study Archaea in the gut are trying to make some connections with, um, health factors. You know, you know, if we look in a population that has a high level of these methanogens, are there certain factors that they are more, um, prone to or less prone to? Are they healthier? Are they less healthier? So that's the area where it's going to right now.
[00:28:05] Russ Altman: Yeah. That's really interesting because of course we also hear about methane in the context of, uh, its effect on, on global warming through the huge amounts of like cattle farming. And other things like that. And I'm, I'm presuming that the cattle methanogens are also Archaea. So, this could have a huge, uh, implication for our understanding of like these big cycles of gas and,
[00:28:25] Paula Welander: Absolutely. And in engineering ways, you know, through like, um, uh, therapeutics for guts, for the guts of the cows, um, to be able to lower the amount of methane that they are producing by affecting their Archaeal microbiome, um, is actually a big area of research.
[00:28:43] Russ Altman: So, so you said that the Archaea don't cause disease as far as we know, but that raised the one issue, question, kind of a random question is, do bacteria that we take kill Archaea?
[00:28:53] Paula Welander: Bacteria that we take kill Archaea? No, I don't think so.
[00:28:55] Russ Altman: So, like if, if I prescribe an antibiotic, I'm a doctor. If I prescribe an antibiotic, do we know if that antibiotic will kill Archaea? Because since they're a little bit removed from bacteria, they may evade. I just don't know if is even known.
[00:29:07] Paula Welander: They don't. Because they're, so, one of the big things that, um, antibiotics target are the cell wall of bacteria and the cell wall of Archaea are different. So those antibiotics, and this is what makes them hard to study because a lot of the molecular work we do requires our bacteria to be sensitive to antibiotics so we can manipulate them in the lab. We don't have antibiotics because they're not bacterial. Um, and a lot of the, um, you know, the mechanisms that they do for like protein modifications and translation, uh, are different. And so those types of antibiotics don't target them. So, we're very lucky Archaea haven't figured out to infect us because we have no way of like actually being able to kill them like we have bacteria.
[00:29:46] Russ Altman: Exactly that, that, that's the, the downside is if they do become troublesome, we're gonna be in big trouble. Okay. Well, that was a great, thank you so much for that introduction to these, uh, amazing, the amazing lipid molecules, the membranes, and then this, uh, really, uh, one of our ancestors, the Archaea. Uh, I wanna move on now before we finish up to our final, uh, segment called the Future In a Minute. Just to review, I'm gonna ask you a few rapid-fire questions, and then you'll give me some rapid-fire answers, and we'll see how it goes. Does that sound okay?
[00:30:15] Paula Welander: Yes.
[00:30:15] Russ Altman: Okay. What is one thing that gives you the most hope about the future?
[00:30:19] Paula Welander: Um, that would have to be my kids and the students that I teach. So, my kids are in college. They're the same age as the students that I teach, and I am just, they are wonderful. They're full of joy. They can hustle. They love life, but at the same time, they're very laid back. And so, I, I get a lot of hope from students.
[00:30:35] Russ Altman: What is one thing you want people to walk away from this episode?
[00:30:38] Paula Welander: Remembering microbes are awesome.
[00:30:41] Russ Altman: Aside from money, what is the one thing you need to succeed in your research?
[00:30:45] Paula Welander: People. Science is only as good as the people who do it. And I need creative, amazing, excited people to come work in my lab. Um, and I need them from all walks of life.
[00:30:55] Russ Altman: If all goes well, what does the future look like?
[00:30:58] Paula Welander: Uh, the future? My future is in a pub, having a beer after riding my bike. But if all goes well, I hope that in the future, more broadly, we have a, um, a, a respect and a love for higher education again, that I think is missing right now. And the people that are in higher education.
[00:31:16] Russ Altman: If you were to start over again and you needed to get your degree or credential in a different discipline, what would it be?
[00:31:23] Paula Welander: I think it would be in something like history or political science. I am just fascinated by how we got to know. And I, one of my favorite podcasts is Throughline from NPR and that connection to the past and the, I'm fascinated with how everything is connected and nothing just happens. And I get to read a lot of books, and I love reading and don't have any time to read.
[00:31:43] Russ Altman: Thanks to Paula Welander, that was the future of lipids on Earth. Thank you for listening to this episode. We now have more than 300 episodes in our back catalog, so you can spend billions of years, no, but a lot of time listening to episodes of The Future of Everything on a wide range of topics that we hope you find interesting. If you're enjoying the show, please remember to tell friends, colleagues, family about it. Word of mouth is a great way to spread the word about The Future of Everything. You can connect with me on many social media platforms. I'm @RBAltman or @RussBAltman on LinkedIn, Threads, Bluesky, and Mastodon. You can follow the Stanford School of Engineering @StanfordSchoolOfEngineering or @StanfordENG.
