Archaea

28:14Your mechanic is going to tell you you need a thicker grade of oil because your oil is going to be too runny in the Sahara and your engine's going to wear out. If you take that same car now to the Antarctic, it will seize up because the oil's too viscous. And it's the same thing at a microscopic level with the proteins in the thermophiles. This may sound like a tangential question, but why are flamingos pink? So this goes to a subject very dear to my heart, which are halophiles. These are organisms, archaea, that thrive in very high salt conditions. So high salt is, imagine you've put too much soy sauce on your Chinese meal.

28:50That's how salty and worse. So the Dead Sea, as Buzz already mentioned, this is where we find them. Saltworks. And if you've ever been to a saltworks or to any of these seas in Australia, they have some great examples of salt lakes there that are bright pink. The bright pink coloration, that's in the membranes of these halophilic archaea. And they form food for some microscopic eukaryotic organisms, brine shrimp, which feed on them. And in turn, the brine shrimp are food for flamingos where we find them. So if we didn't have the red coloration in the halophilic archaea, we wouldn't have pink flamingos.

29:33And it's also why if you buy Himalayan salt, it's pink, partly because of the archaea. So we're eating archaea when we eat Himalayan salt. Krista, where do we see the impact of archaea in the ecology, in the environment, in the ground, in the atmosphere, in water? Yeah, so this is also important to mention because archaea are very interesting for the adaptations and evolutionary aspect, but there's also a big aspect of ecological effects on Earth. And the one group is the methanogenic archaea. These were the ones that Carl Wosz first investigated, by the way, when he found out about the relationships.

30:11And methanogenic archaea are almost everywhere, but they don't like oxygen. So they are in all anoxic environments, in the marine sediments, in a lake, down in a lake bottom. They're also in our gut system, right, where there's no oxygen in some places. And these methanogens are important for ecosystems because they are at the end of the food chain. They use the very last products from bacterial and fungal degradation and convert it into methane, which is again a food for other bacteria when it bubbles up, you know, it's a gas and then it comes up and it's the food again for bacteria to degrade it further on.

30:50So it is an important part in the, we say, global biogeochemical, carbon cycle. But it is also problematic because with global warming, methanogens in the Arctic soils where the permafrost is thawing, or methanogens in wetlands around the equatorial area, they are producing more methane now. They become more active. And methane is a very strong greenhouse gas, and it is responsible for, there are debates, but 25 to 30 percent of global warming effects because it's a very strong greenhouse gas, 30 times stronger than CO2. So that is one group that is important to look at. They also have a lot of good sites.

31:30You can also make biogas from them, which is also the same thing. But yeah, one has to keep an eye on them, one could say. And the other group is ammonia oxidizing archaea that occur or that are found in many soils and in the ocean and virtually everywhere where you also have oxygen. So they also occur, they also live on our skin, actually. We have just isolated an organism from our skin, but they are good. They are good for our skin, we think. We have not proven that. But these organisms are involved in the global nitrogen cycle, which has to do with fertilization, how we produce food, and fertilizer is escaping into the surface waters.

32:11And part of this problem can be traced back to archaea that feed on these nitrogen compounds or to also certain bacterial groups. Yes. And can any of you chip in on cattle, methane and archaea? I can. So Krista already mentioned where methanogens, these archaea that produce methane, they live in our gut. They don't just live in our gut. They also live in the guts of cattle. And we have a much bigger consequence when we look at cattle metabolism. So what are they doing in there in the first place? So Chris already mentioned that they feed off the end products of bacterial fermentation of products that we cannot digest.

32:51So it's principally dietary fiber that we cannot digest directly that bacteria then ferment. The end products of their fermentation, hydrogen and carbon dioxide, are turned by these methanogenic archaea into methane. And we emit about 350 millilitres of methane every day. But that pales into insignificance compared to cows, which put out about 200 litres of methane a day. And given that methane is 20 times more potent than carbon dioxide, we now have a big problem on our hands. Talking about food cycles, what's the favourite food of some of the archaea you study? I think we all have to chip in here.

33:30Let me start then with halophiles that we grow in my laboratory. These have a very simple diet in microbiological terms. because if you're a microbiologist and you don't know what to feed something, you feed it powdered marmite, yeast extract. Nearly everything grows on this, nearly everything. They then have some additional requirements on top of that. Well, the thing in a way, though, is that because these microbes live in communities, and as we heard from Asgard, they have to live with other cells to actually survive. You know, you could have two cells living together where one likes the marmite, the other doesn't, but that one can use the marmit and release its waste products which the other one can then use in turn.

34:12So this is the sort of principle of symbiosis which archaea and all microbes, in fact, engage in all the time. So our idea about individual organisms living by themselves, fighting each other, is wrong in that sense that food can be shared by different organisms. I've got to say, I can't help but notice the tremendous enthusiasm that researchers working with archaea, the enthusiasm they express, but these things are very hard to study. I mean, if you've got something living at 95 degrees or more, how do you get them back into the lab and look at them? It's incredibly hard. And in order to work on them properly, my lab had to ditch everything else we were working on, flies and human cells, to work on our care, because each one requires devotion.

34:59You have to really love them to get them to grow, some more than others. but the thing is it's so rewarding because they haven't been studied we don't know how to grow that means that when you discover things with them they're completely new but my lab for example in the last few years spent five years trying to build a microscope that will work at 75 degrees centigrade which if you touch it you burn your hand which is ambient for these organisms from Yellowstone National Park that grow in these sort of sulfurous volcanic springs and then we had to We evolve proteins we can put inside that emit light so we can see how proteins move in these things.

35:37So these things, for a bacterial cell, a human cell, were done decades ago. But for archaea, if you want to do anything at all, you have to invest huge amounts of time learning to nurture them, love them, and then find ways to engineer solutions so you can actually study them. Did you succeed in inventing the 75 degrees? Yes, and the trick is to heat the lid. Congratulations. Congratulations. Krista, Buzz has told us about how you look at them in the laboratory, but how do you go and get them in the first place if they're in Lockie's Castle down at the bottom of the sea? How on earth do you find them?

36:13Good point, good point. So to get them from Lokis Castle is of course with a submarine, you know, with an ROV, they have been taken. But those are also difficult to work with and we have not succeeded yet to culture them from Lokis Castle. but we are using shallow marine sediments and there also we take care that we keep them without oxygen. So we bring them in a little tube, we bring them home to the lab right there at the site where we take them and then we inoculate, we put them into new flasts and try to grow them right away and try to avoid oxygen right away. That's one thing. But then there's also other archaea, for example.

36:53I have also many years ago isolated one of the most acidophiles which means an acid lover. So if you isolate an acid-loving archaeon, you need to be very careful how to bring it home because it will be killed, because it needs its own activity and metabolism to be able to cope with the acid. And so you have to shift a little bit away, you have to dilute out the acid a little bit, but not kill it because it needs acid also. So you need to find compromises. And there's an interesting story from the 1980s when the first archaea were discovered as such from Calvaux, then people went out, people like Wolfram Sillig, who were strong proponents of Calvus' idea because of their findings.

37:33And they went out to get novel organisms from hot springs and they brought a thermobottle, you know, at the beginning because they thought you have to keep them warm. You have to keep them like they are in the warm water. But that was not true. They are actually happy to get cooled down because then they become more inactive. Then they are like we would be frozen, kind of. So it depends. So I have to say, though, not all archaea are that difficult to work on. So traditionally, if you have wanted to work with the organism in the laboratory and do some more complicated genetic experiments and not spend all of your time and energy like Chris and Schlepper and Buzz here trying to keep them alive, you work with halophiles.

38:16What do you need besides Marmite? You just need a lot of salt. Pour in salt until it becomes almost saturated. and actually conversely if you want to decontaminate something if you accidentally spill some of these halophilic archaea on the bench wipe it down with water it kills them yeah but you have other problems with your halophiles because it's very hard to do biochemistry for example well it and electromicroscopy is very hard okay so there's no perfect species um yeah so it turns out that what krista is referring to is that the way that halophiles cope with high salt is they have salt inside the cells as well as outside.

38:53And it means that all of their enzymes have to be able to function in very high salt concentrations, which brings with its own challenges, including for us, if we want to study those proteins in the laboratory using biochemistry. So I avoid doing biochemistry. You mentioned a little earlier on about the fact that they live in our gut in an anaerobic environment. Now this is, I'm going to confess my huge ignorance here. I didn't realise things could live without oxygen, but most of these archaea apparently seem to thrive outside of an oxygenated environment. Why is that? The answer to that is partly because the enzymes they use to make methane are poisoned by oxygen.

39:40So they have to grow without oxygen. You only find them in environments like our gut, like land for sites, like swamps, where, in fact, the first person to ever discover methanogens was Alessandro Volta, back in the 18th century, from whom we also have the term volt. And he was poking around some swamps in northern Italy and noticed some bubbles of methane coming up. And arguably, he's the first person to have discovered methanogens. Because they caught fire, right? They caught fire, yes. You can light fire to methane. Buzz, you were going to come in there. Yeah, I mean, also we have to remember that, you know, we call archaeo-extremophiles, but of course they think we're extremophiles.

40:20And one reason, for example, to make that distinction is for most of Earth's history, there was no oxygen in the atmosphere. And so for two billion years, archaeo-bacteria were living on a planet with no oxygen. And in fact, the increase in oxygen about 2.5 billion years ago, made by cyanobacteria doing photosynthesis, changed everything, led to a catastrophe in a way that lots of things that couldn't live with oxygen suddenly died. And archaea had to hide away in these places which are still anoxic, like in our guts and in sediment. But this also meant that at the margins you could have new evolution, new things like complex cells.

40:57So, Krista, did complex cells come because oxygen suddenly appeared? Yes, this is probably the case. Yeah, this is probably the case. So the idea at the moment, there's a little bit of a debate what the Asgard archaea, the exact Asgard archaea that maybe we are looking for that were existent two billion years ago. We cannot find them nowadays, of course, but something similar. If they were, how much they were already adapted to the first oxygen and how much they actually then profited from engulfing a bacterium that was already coping with oxygen. and because why did life expand so much with oxygen also?

41:37The new forms of life that could cope with this is because you can gain a lot of energy when you have oxygen involved, right? When you can breathe oxygen and not other chemicals. Which is why we burn hydrocarbons in oxygen, you know, to drive planes and cars for that reason. It generates a lot of energy. Let's have a final question. Bacteria, we have good bacteria and we have some very bad bacteria. Do we have good archaea and bad in terms of their relationship with us, pathogens that cause disease? So we have archaea that grow inside us in our gut, as we've already mentioned. And it's a big mystery in the field why none of these become pathogenic, cause us any disease, because we have bacteria that grow in our gut, which if they can then overtake the good bacteria, cause us all kinds of gut problems.

42:30This doesn't seem to be the case with archaea. Now, why might that be? One thing that we've not touched on so far is that archaea have, on the outside of the cell, a fundamentally different membrane structure to the one that we have and that bacteria do. And that different membrane structure both gives them extra thermostability, allows them to colonize high-temperature environments, but it might also make them a really good target for our immune system. Buzz? Yeah, I mean, I think as Torsten said also, I'm not sure we know the consequences of archaea for our health. We know we've been living them for a long time because when they looked at the DNA on the teeth of Neanderthal skeletons, they found the same archaea that we have on our teeth.

43:12So ancestors are not just making babies together, also kissing and sharing food maybe. But it means they've been living with us a long time. They're in our guts. When we take antibiotics, it kills the bacteria, not the archaea. But when you take statins, actually, it kills the archaea. And there are no studies. We don't know yet, I think, the consequences. So it's true that archaea, there are no diseases we know about, and they do grow slowly as well, and they might be seen by the immune system. But I think, watch this space. Who knows how important they might be for our health? Actually, on that point, just very briefly, Buzz, you can take statins to cure constipation due to excess methanogenic archaea.

43:50Well, my huge thanks to Krista Schleper, Buzz Baum and Thorsten Ehlers. Next week, it's Dadaism, the nonsensical chaos that emerged in the Zurich art world during the First World War. Thanks for listening. And the In Our Time podcast gets some extra time now with a few minutes of bonus material from Misha and his guests. Well, and now we can go over to the podcast thing. I have to tell you, I'm going to be honest here. I had no idea. I didn't even know Archaea existed. and as I was doing the research for the programme, my jaw just dropped further and further down. It's absolutely fascinating. You're not alone.

44:38Most scientists don't know they exist either. And they can't pronounce our care either. Most of my colleagues don't know. Maybe the problem is actually the name, that they are not so famous. I don't know. Yes and no, I don't know. It's a good name? Okay. So what else have we missed out? I mean, I think the key thing for me and what I was trying to understand is that relationship between our cell structure and their cell structures, or at least what we share in common with them. Do we have a similar relationship to bacteria? Well, help me, please. So it depends on your perspective. That's true.

45:22So from my perspective... I have a stompers. OK, you start. My perspective here is that I work on DNA replication. So how we turn one molecule of DNA into two molecules of DNA. Why do we even have this two-step process of turning DNA into RNA and then RNA into proteins? Because DNA is more stable. But if you wind back the clock, we all now think RNA was the original genetic material. So it must have been an RNA polymerase that made new copies of RNA. So it preceded DNA? It did. Because RNA, as well as being able to code for itself, can do catalysis. Something that DNA can't do. It's just down to a single oxygen atom.

46:06This is where we have deoxy. Just explain catalysis for us. So catalysis is, you can have non-enzymatic catalysis. That's chemical catalysis. It means speeding up a reaction. So something that won't go... As in catalytic conversion. So, for example, a piece of wood won't burn because it just sits there. But if you add a catalyst like you heated up, suddenly you get a flame. Yeah. So, for example, the platinum in your cast catalytic converter, that's a chemical catalyst. Right. But you can also have an enzymatic catalyst, so it'll speed up a biochemical reaction. RNA can do that because it's got an oxygen atom on its backbone that's very reactive.

46:46DNA is lacking this. So it can't do catalysis, but that, on the other hand, makes it much more stable. And that's where we have this now split of things. But when it comes to archaea and the enzymes that make new copies of DNA and new copies of RNA, there's a really fascinating discovery that came out about six, seven years ago. The DNA polymerase that makes new copies of DNA, there's a version of this enzyme that we find in archaea and only in archaea. And at its core, the bit that does all the work looks like a dead ringer for RNA polymerase. So if we trace the clock back to the beginning of life, RNA was there first, being copied by RNA polymerase.

47:33When we now make that leap to DNA polymerase, perhaps this is still the DNA polymerase that did that first bit of DNA copying. And we only find it in archaea. We find bits and pieces of this DNA polymerase now in us, in eukaryotes, but it's since been supplanted by other more efficient enzymes. But when it comes to quantity of genes or enzymes that we share with eukaryotes, or with archaea, that us eukaryotes share with archaea, then it is not so many. It is because you think, Torsten, and I agree, that information processing these events are maybe the most important in a cell. But if you argue from a metabolic point of view, how we gain energy or things like this, then actually there is a lot from the bacteria in us.

48:23So mitochondria, for example. Can we explain about mitochondria? Because it was introduced as a concept, but not everyone. Yeah, so the complex cells, eukaryotic cells, have these two, we think, at least contributing organisms, an archaeal cell and a bacterial cell. And the bacterial cell is the one that then acts a bit like a bacterial cell living in oxygen. It will burn hydrocompetent oxygen to generate energy, which then it gives to the whole. And the rest of the cell, a lot of the machinery, as we said, comes from the archaeal side. Now, you can look at the two and sort of look at it like an equal partnership.

49:01But the truth is, when you look at a eukaryotic cell, one of our cells down the microscope, there is a bacterial-like mitochondrial sitting there, which is why Lynn Margulis said there's a bacterial cell living inside. And other people had seen that before for chloroplast. It really looks like a bacterial cell. The rest of the cell looks completely alien, like this, you know, where did it come from? Woes didn't think it came from, you know, thought it had a sort of a separate lineage. but now we know that there are archaea which as chris sort of said have many of the things that we thought had never been seen before in any prokaryote so for example we my lab we would argue we've now seen even compartments with inside archaea they have long protrusions they move chris's lab is showing they can move but also the information uh that they contain is is is in case sort of in a hub at the middle and they have these long protrusions which are a bit like the edge so very much like our cells we think they have spatial separation between information storage and execution so what archaea do is they change the way you look at cells because before the discovery of ascarlochea you couldn't really see the origin but now we're learning to look afresh at these archaea cells and see in them maybe a protonucleus maybe a protocytoplasm maybe you know cell motility maybe compartments that resemble the compartments we have in our cells So suddenly these ascal really are like a stepping stone from simple to complex that give us clues about how it works.

50:28But of course, the eucalyptus cell really requires the mitochondria. So you might have a very complex archaeal ancestor, but until the mitochondria came on board, it wasn't this amazing thing that can make a bird of paradise and a mushroom. And we should maybe also refer to the other studies that argue maybe there were more partners because there's more bacterial-type genes in our cells that might have come earlier. There is a way of doing that, just transferring one gene by the other, not by such a big merger, but by individual processes. And this has also been hypothesized. Right. So the archaea, sorry, are very much like a blended family.

51:06And we inherit not just genetic components by vertical lineage, the way that we like to think of a family tree, but also we acquire them laterally by genes which have been traded between cells and sometimes hitchhiking on viruses. So they speed up evolution in this way. I mean this in a way was one of Woese's, again, one of his brilliant insights is that if you look at actually all organisms on Earth, bacteria in our care, actually genes move all the time. And that's why people in hospitals get these, you know, antibiotic resistance because these bits of DNA jump. But Woz realise that the one thing that doesn't jump is this core information stuff.

51:44And that is inherited as cells grow and divide in two and their daughters grow and divide in two. So in a way, although there's been all this mixing of genes, there's a one-cell lineage on Earth. There was once a cell and we are all its progeny. And it gave rise to two branches, archaea and bacteria. And each of those cells grew and divided. It's a single lineage which then fused to give rise to eukaryotes. Two billion years later. Two billion years later. It's a wonderful story, actually. It goes like this. Good God. So, Krista, so we have three branches, also known as three kingdoms. You mentioned a researcher who you worked with, Wolfram Zillich.

52:22Why was he so distressed about the three kingdoms? Yeah, this was at the time when... Not just him. Not just him, maybe. That was at a time when these kingdoms were also called Reiche, the Reich or the Urreich even. So the Reich meaning empire in German, of course. Yeah, also exactly. And then when he heard about that, there was this researcher in Illinois who had found a third Reich of organisms. He was not pleased. It was in the 1970s, 80s. And he was a committed anti-Hitler right. Yes, he was very committed. So that's a rather unfortunate name, the Third Reich, particularly as it's describing something that is just so dramatically wonderful.

53:11Yeah, but now we talk about domains. So that has been solved. So we're back. We're good. Domains, the third domain. That's good. It's almost time for a cup of tea. But I, you know, I mean, I've in the short space of time, I have learned so much about which I knew nothing. This has been a fantastic discussion. And thank you very much for everything. Buzz, do come in there. I just want to say one thing I just wanted to say maybe that I think is so exciting about RKO research is because it almost changes the way. So everything you learn in a textbook when you start working on RKO, it all falls away.

53:49but it also means that you start to realise it's not survival of the fittest. Things can live together. They can also affect ecology. So you have to look at cells in light of evolution, ecology within the world. So for me, it is like also our care researchers are the ones who are studying life in the environment in an evolutionary context, which is, as Woes would say, I think, proper biology. Simon. Who'd like tea and who'd like coffee? Tea, please. Tea, please. Or teas. Thank you very much indeed. Thank you. Thank you very much. Thank you. Thank you. In Our Time with Misha Glennie is produced by Simon Tillotson and it's a BBC Studios production.

54:28Hi, we're the Van Tullican, the identical twin Dr Van Tullican's Chris and Zand. In What's Up Docs? We're diving into the messy, complicated world of health and wellbeing. We are living in the middle of what I would call a therapeutic revolution, but it can sometimes be hard to know what's really best for us. Do I need to take a testosterone supplement? How can I fix my creaky knees? Why do I get hangry? Is organic food actually better for me? We're going to be your guides through the confusion. We'll talk to experts in the field and argue about what we've learned and share what we've learned and maybe disagree a fair bit too.

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