 Hello there, can everyone hear me at the back? Yep, great. Okay, well I'm a biologist, so one of the advantages of that is that there'll be no equations in my talk, so hopefully you'll understand it. We'll see as we go through. And today I want to share with you about bacteria. And the first question is what are bacteria? What is a bacterium? Well this is a bacterium, it's a single celled organism. And what I'm really interested in is the thing in the middle, the DNA. And hopefully you'll learn a little bit about that today. Okay, so why should we care about bacteria? Is my first question. And the first answer is because there's a lot of them. Five million trillion trillion bacteria, something like that, on planet Earth currently. And particularly interesting for us is that a lot of them are actually inside you. So your average guy, Bob, let's say, he's made up of around 30 trillion human cells. But within him, within Bob, we find there's actually 38 trillion bacterial cells. So technically he's more than half bacteria, at least on a cell count. But the bacteria are quite small, as you probably know, so they only weigh a total of 200 grams. So we care about them, cause there's a lot of them, but there's not just a lot, but they actually influence us in all kinds of ways. And there's lots of studies that are coming out recently about the connection with health, so lots of different things, our immune system, various diseases, and lots of supposed links between the bacteria in our gut and our health and how we live. But I'm particularly interested, not just in bacteria, but how they change. So this is the study of evolution. And evolution, first up, is this big picture idea. So it's the tree of life. But it's not just the big picture, it's also the process, or it's a process. I think the wrong slides are actually put up, but I'm not sure if that's changeable, I'll deal with it. Anyway, so this is the main process in evolution, is the process of natural selection. And that's how nature weeds out variation, which we have. So there's variation in nature. In this case, there's different colored insects. But nature can sort through that variation and produce change in the population. So you see that the distribution in the population changes over time. So it starts that there's a few green bugs, but if predators tend to select those, then there'll be fewer over time. And that's just evolution, it's a change in the population. And okay, so in general, it's changes in populations, but you can particularly change, or you can particularly study it in bacteria. And the way that, one way that this has been done is in flasks, so this is on the left. It's a very simple system, it has some culture, some material for the bacteria to grow in. And if you transfer a small amount for one flask, the next flask, the next flask, the next flask, every day for thousands of days, then you can see a lot of change over time. And this is one major study that's been done. And we are going up the y-axis, we have fitness, so it's basically a growth rate. And along the x-axis, we have the number of generations. So this study has now actually gone for 70,000 generations. This was just partway through. And basically, all we see here is an increase in the growth rate. And particularly interesting in bacteria, particularly important for us, is the study of antibiotic resistance. So when we use antibiotics to try and kill the bacteria, this changes again, as before with the bugs, this changes the population. So if we particularly don't use enough antibiotics, there's some that are still remaining. Some of these could be the ones that are remaining will tend to be more resistant. Over time and in different circumstances, you can get a huge growth in antibiotic resistance. And this is a huge issue for health at the moment. So people are saying it's the next apocalypse, or it's the next pandemic, it could be the apocalypse, worse than cancer, all of these really severe headlines. But it turns out we can actually, it's not just this kind of theoretical threat, but we can actually observe it. So if we start with this, so okay, so firstly, imagine a petri dish. Does everyone know what a petri dish is? It's just a small plate with gel in it that bacteria can grow on. And one study that's been done at Harvard University uses a huge petri dish, which is the size of a large table. So it's three meters long. So this is the petri dish. And it either ends, you have bacteria placed, but bacteria can't grow in the middle because of antibiotics. But over the course of a few days, you can actually see the bacteria starting to grow into the antibiotics. And that's because of evolution. So there's genetic changes in the system that allow the bacteria to grow. And over the course of a few days, you'll actually see it cover the whole, so I don't have the picture here, but it'll cover the whole table-sized plate. So this is the process of antibiotic resistance in real life. So evolution is a big picture, a story of life. It's a process, natural selection, but it's also observable. And one of the results or one of the results of this process is how antibiotic resistance actually occurs. And it occurs by what's called a trade-off. So quite often when you become more resistant to antibiotics, you lose something in the process. So by gaining an evolution, you quite often lose. Evolution is quite often a short-term, easy fix kind of process. And this graph just shows that the vast majority of mutations we know that cause resistance actually also cause a decrease in fitness for the bacteria that are involved. So most of them are on the left of this graph rather than the right. And I just wanna quickly explain to you how this happens. And it happens, this trade-off process, imagine a car, so it's a very complex machine. It has all kinds of parts. Some aren't necessary in some environments, but are in others. So if you want to drive the car through a desert, there's a bunch of things in there you probably won't need. You can chuck out the heater and it would be fine. But then if you move into a cold environment, you'll want that heater. So this is kind of what happens in evolution. The easy fix that makes the car more efficient will quite often happen. So just through chance events, the bacteria will tend to chuck out the stuff it doesn't need. And yeah, so this happens and this means the car is less fit ultimately, which results in this kind of situation. Okay, I wanna quickly talk through one specific example of this. And this is how resistance antibiotics occurs with different antibiotics. Okay, so one important antibiotic is called streptomycin. It's a kind of amino glycoside. And it turns out that the way that resistance to this antibiotic occurs involves something called a proton motor force. So we've got to start at the start with the structure of the bacteria. What's around the outside of the bacterium? Anyone? A membrane, sure. Okay, so this is basically what we've got here. And across the outside of this membrane, a lot of processes can occur because of a chemical difference across that membrane. And it turns out that different antibiotics use this chemical difference. This is called the proton motor force. In order for that, okay. And one, so the streptomycin requires this difference. And it gets pumped across the membrane. So it gets pumped from outside to inside using this proton motor force. So resistance to this antibiotic tends to happen by reducing the proton motor force. That's fine, but most other antibiotics actually require most other antibiotic resistance actually occurs by pumping things outside the cell. So different drugs like penicillins can be pumped out with the use of the proton motor force. So if you use both, basically, if you use both of these drugs in combination, the bacterium has a real problem. Because in order to try and adapt to one, it tries to reduce the proton motor force. But in order to adapt to the other, it needs to increase or use the proton motor force. So the moral of the story is if we understand evolution, we can actually prevent it happening or limit it or kill the bacterium much more efficiently. So using two drugs at once is a trick that we've learned by studying the kind of mutations that happen in evolution. So in conclusion, if we really want to understand these processes and survive the growth of the superbugs, it'll be a really good idea to understand bacterial evolutionary genetics. Thank you. It wasn't the right slides. So I think the best solution is just understand these processes better. So if we understand how the bacteria are adapting to our antibiotics, we can actually use the right combinations and prevent most of the problems that way. You know, some people are saying that, but there's huge kind of debate within what we're trying to question. Yeah, yeah, so I think we'll be fine if we understand the processes and use them carefully. So if we use them in a more targeted way, at the moment they're kind of just given out quite generously. If we use them together in very specific combinations, then we can kill the vast majority of the bacteria. There will be some that will be resistant and won't be treatable, but I think that won't increase significantly if we're careful with it. That's, yeah, that's my take. Yep, there's one at the back. I don't think so, unless they're transferring it to you, yeah. So everyone has their own gut microbiome and I don't really know how much of that is transferred. It just depends how close you're getting to other people, I guess, but yeah. I don't know, just as far as possible, probably, but.