Jayme Dyer (MIT): Knowing Where to Go: How Cells Drive Without Eyes

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Lots of good science in this lecture.

๐Ÿ‘๏ธŽ︎ 2 ๐Ÿ‘ค๏ธŽ︎ u/John-AtWork ๐Ÿ“…๏ธŽ︎ Jan 20 2016 ๐Ÿ—ซ︎ replies

Jayme Dyer provides a simple to understand explanation of how cells move around the body, and how they know where to go.

Found it on the iBiology channel, a must for anyone interested in biology.

๐Ÿ‘๏ธŽ︎ 1 ๐Ÿ‘ค๏ธŽ︎ u/MinisTreeofStupidity ๐Ÿ“…๏ธŽ︎ Jan 20 2016 ๐Ÿ—ซ︎ replies
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Hi, my name is Jayme Dyer and I'm going to tell you about the work I did as a PhD student at Duke University. I'm a basic cell biologist, which means I'm interested in how cells perform complex behaviors even though they don't have brains. And specifically what I did for my PhD is study how cells are able to drive without eyes. And I don't mean that they get into a car and they drive away, I mean that they go in a particular direction to find a target. Now a really good example of a cell type that can do this is sperm. Sperm are really good at finding eggs, and yet, obviously, they don't have a brain and they don't have eyes to see where they're going. But they're really good at finding eggs. So, it turns out they use a mechanism to find eggs that's very similar to what many different cell types do. A process called gradient tracking, and I'll tell you what is in a second. Another type of cell that can do this is white blood cells. So, when I cut my finger this fall cutting sweet potatoes, I opened the skin -- unintentionally, and introduced bacteria from the environment into my body. Now the reason why I didn't get an infection from those bacteria is because I have white blood cells whose job it is to go around my body and engulf bacteria to remove them. Now, not all of the white blood cells in my body live in my fingertip, they live all over. And their job is to go to wherever the bacteria are whenever bacteria get introduced. Now, they use a similar mechanism as the sperm in order to find the bacteria, but again, they don't have eyes or brains. So that mechanism is called gradient tracking. And to explain it, I want you to imagine that you walk into your friend's house, and your friend is baking cookies. Now you've never been in his house before, so you don't know where his kitchen is. But you can smell the cookies baking. So the first thing you're going to do when you walk in is sniff, and you're going to sniff, and you're going to go in the direction where there's more cookie smell. So it turns out that the sperm and the white blood cells do exactly the same thing. So in the cookies, the cookies are actually when they're baking, they're emitting a chemical -- actually a number of chemicals, that are diffusing away from the cookies. So in the oven, the cookie chemical is diffusing away and as it gets farther and farther away from the cookies in the kitchen and in the living room, the number of molecules decreases because they're spread out by diffusion. And so when you walk into the house, you smell the cookie smell and the closer and closer you get, the stronger that smell becomes. So the white blood cells and the sperm are doing the exact same thing. Eggs and bacteria secrete chemicals that diffuse away in the environment and the sperm when it's trying to find the egg, is essentially sniffing that egg smell. And saying, "Oh! That's good!" and trying to get to the egg. So, to give you an example to show you a cell actually doing gradient tracking. So let me go back, the gradient is the gradient of the chemical, and the tracking is finding is tracking that target. So here's a cell doing gradient tracking. This is a type of white blood cell called a neutrophil. And that's the funny shaped cell in the middle. And all around are these red blood cells because the -- because this was taken from a blood sample. And the funny shaped dumbbell cell is the bacterium. And you'll see that this neutrophil is really good at tracking the bacteria. In fact, it's so good that even as the bacterium moves around, the cell is able to reorient, and that's actually a really important characteristic for cells doing gradient tracking. The other thing you'll notice is that the cell has a very distinct front and back. Oh! They got it! They're very good at doing this. Okay, so like I was saying, the cells that do gradient tracking have a very distinct front, you can see that here. It's very different than the back of the cell. And that's basically an indication that the cell has cell polarity, there's a a difference from one side of the cell to the other. And I'm going to talk a lot today about cell polarity, the front and the back. And these cells when they're doing gradient tracking always put their front up gradient, trying to get closer to the chemical smell. Now, how is it that cells do gradient tracking? Well, like us, they have noses -- sort of, they don't actually have noses, they have proteins called receptors that bind specifically to the chemical. And actually, what's interesting is that the receptors that these cells have to sense the chemical is exactly the same type of receptor that's in your nose when you sense the cookie smell. So in this schematic, the cell has receptors all over it. And the receptors bind specifically to the chemical. And what's different for cells that do gradient tracking versus us, is that we only have one nose. So when we walk into the room, we have to sniff over here, and over here, in order to get a sense of where the most cookie smell is. But cells, because they have receptors all over them, they actually can take one sniff and get a sense of where the gradient is. So they got receptors all over the cell surface, and they can go *sniff* and get a sense of whether there's more receptors bound to the chemical on this side or this side. Now in this example, it's really easy because the most number of receptors that are bound to chemical are on one side. And so the cell knows it needs to go in that direction. But in most cases, when cells are doing gradient tracking, they're doing it in an environment that looks more like this. Where there's a very small difference from one side of the cell to the other, and the number of chemicals that are bound to the receptors. So in fact, we know from studies in a variety of cell types, that cells are good in doing gradient tracking with as little as 1% difference in the number of receptors that are bound to the chemical on one side versus the other. And in fact, 1% is like if this side had 100 receptors bound to the chemical, this side has 98 bound to the chemical. So at this point, you might think the cells are just really good at sensing the difference from one side to the other, and we think they are. But there's one other complicating factor. And that is, in my schematic, all of these chemical molecules are stuck to the screen. But in reality, they're actually bouncing around because of diffusion. And so these molecules are falling off and coming back on and sticking to the receptor and falling off. And that means that there's a lot of what I'm going to call molecular noise. And that's a problem for the cell because if the cell takes one big sniff at any one moment, then there might be just because of noise and random chance, there might be more receptors bound to receptors on the down gradient side than the up gradient side. And so if the cell simply took that snapshot, it would think it needs to go in the wrong direction. So cells need some way to ask over time, what the concentration is on one side of the cell versus the other, of the chemical that they're sensing. And I was really intrigued by this question, how do cells overcome molecular noise? We know they do, they're really good at it, how do they do it? So, that's the question I set out to answer. But I wanted to do it in a system that was a little easier to work with than white blood cells or sperm. So I decided to work with the budding yeast, Saccharomyces cerevisiae. Now Saccharomyces cerevisiae is the same type of yeast that you use to make bread or beer. And is very genetically tractable, what that means is it's very easy to make mutations or changes to the genes which allows me to ask very specific questions about how is it that the cell does specific things. Now there are a couple differences between yeast cells doing gradient tracking, and I'll tell you how they do it in a second, and white blood cells and sperm. And one of the most notable is the fact that yeast cells are a fungus. And that means that they have a thick cell wall around them, sort of like plant walls but it's a different material. But that means that they can't move, that will be important in a second. So, when do yeast cells do gradient tracking? They do it when they're mating. And if you've never heard about yeast mating before, which it seems like most people haven't, because most people don't think about yeast mating. Let me explain when it happens. So yeast like you and I, can exist as diploid, so they have two copies of every chromosome. And they can proliferate and make more cells as diploids, just like how our cells can proliferate as diploids. They can undergo meiosis, which is the process that we do in our gonads to produce haploid cells that have one copy of every chromosome. Now unlike us, where we have sperm and egg, and those cells can't divide until they come together to create a diploid, yeast cells can actually divide, they can proliferate as haploids. So that means when you're making bread, in your bread dough, there might actually be some haploid cells that have only one copy of every chromosome, and they're just dividing away and happily living their lives. So haploid cells come in two types, a and alpha. And a and alpha cells eventually at some point, if they find each other, they'll come together and physically fuse, just like an egg and a sperm, in order for their nuclei to come together to create a new diploid. But I told you that yeast cells, because they're fungus can't move. So when they are -- so how is it that they get near enough to each other to physically fuse? And the answer is that they grow towards each other. So if I'm a yeast cell and I have a mating partner over there that I want to get to and we're not touching, I'm actually going to grow, sort of like they're reaching out to get to their mating partner. And again, how is it that they know where their mating partner is? We know they're really good at orienting this growth in the right direction, but they don't have eyes. So they use the exact same process that white blood cells and sperm use, in that they do gradient tracking. So it turns out that a cells constantly secrete a small molecule that diffuses away from them, it's called a pheromone. And alpha cells find that smell very sexy. And if they smell that pheromone, if that pheromone binds to their receptors on their cell surface, they'll make a projection up the gradient to try to find that a cell that must be nearby. And vice versa, a cells respond to alpha -- the alpha pheromone. So that was the system I was going to use to study gradient tracking. And just as a proof of principle, let me show you that yeast cells actually can do gradient tracking. So in this movie, I'm showing you a cells that I've put in a special slide called a microfluidics device. And with that special slide, I'm applying a gradient of pheromones, so that there's the most amount of pheromone on top and the least at the bottom. I'm basically tricking these cells into thinking that there's a really big sexy alpha cell up here, and they should reach up to try to get to it. Of course there aren't any alpha cells around. I'm just applying the pheromone. So you'll see in this movie that as the cells grow, they grow up the gradient. And in fact, there are a few cells that can reorient. So they weren't -- so this one wasn't able to go up gradient because a couple cells were in its way. And this one went in the wrong direction originally. So just like the neutrophil, the cells are able to reorient if they go in the wrong direction. Turns out they can reorient if the gradient changes. I'm not showing you that here. And they have a polarized morphology. There's a front, so they're growing only at the tip and the back, which is where they're not growing from. So, just like the white blood cells, I now have a system that I can study gradient tracking using yeast. Okay, so going back to the problem of how cells deal with molecular noise. The problem is that at any one moment, they might have the wrong sense of which way the gradient is, because due to molecular noise, there might be more receptors bound to the chemical on the down gradient side than on the up gradient side. So one of the ways that we think cells that can move like neutrophils and sperm deal with that, is that they do something called a biased random walk. And the idea here is that they take a sniff and maybe they're right, that the most number of receptors are bound to chemicals on the up gradient side, or maybe they're not. But it doesn't matter, because more often than not, the up gradient side will have the most receptors bound to the ligand or bound to the chemical. And so even though they won't always be going in the right direction, net they'll go up gradient. So over time, they'll end up going in the right direction. So that's a very nice theory about how cells that can move do gradient tracking. But it doesn't work for yeast because like I told you before, yeast can't move. So the first question that I have is how do yeast do gradient tracking? They can't do a biased random walk because they can't walk. So how do yeast do gradient tracking? So to try to answer that question, the first thing I did was I looked inside the cells. And I did that using a fluorescent protein. So I fused GFP, the fluorescent protein, to one of the proteins that localizes to the cell front, that protein is Bem1. And Bem1 is what I'm going to call a polarity protein. Obviously it's involved in the polarity of the cell. And in fact, it and a host of other proteins, are localized in a patch -- and I'll talk more about the patch in a minute, localized to a patch at the front of the cell. And in fact, wherever that patch is, that's where growth is happening. So in this movie, you see the cells, the outline of the cells as they're growing in a gradient. So I'm applying a gradient, so again there's pheromone from the top, highest at the top. And here, we're looking at the fluorescent protein, Bem1, which is fused to GFP. And what you'll notice, what I noticed when I looked at this movie is that the polarity patch, the Bem1-GFP patch of proteins is very dynamic, it seems to wiggle around a lot. And in fact, in this montage, we're looking at just one cell. And we're looking at the tip of the cell, and you can see the polarity patch seems to wiggle from one side of the cell to the other over time, as the cell is tracking a gradient. So this immediately evoked for me the hypothesis that maybe yeast do do a biased random walk. Except, of course, the yeast cell can't do it. But what if the polarity patch, what if the proteins that say "This is the front, this is where growth should happen." What if the polarity patch does a biased random walk? So the white blood cell itself can move, but what if in yeast the polarity patch is wiggling around and wherever it is, that's where growth is happening. And if somehow the polarity patch was able to be biased by the concentration of pheromones on the outside of the cell, then it would spend the most amount of time on the up gradient side of the cell and where the polarity patch is, that's where growth is happening. And so that would result in net growth in the up gradient direction. So that was my hypothesis, that the polarity patch does a biased random walk. Now I'm a geneticist, so the way that I want to test this hypothesis is that I want to mess with it. I want to mess up the wandering. In fact, what I'd really like to do is stop the wandering. Because if I'm right, that the polarity patch does a biased random walk, then if I stop the polarity patch from wandering, I should stop the cells from being able to orient in a gradient. Now that's what I want to do and I'm actually gonna do it. But I'm not going to get to it until the end of my talk. Because in order to do that, I need to understand what causes the polarity patch to wander in the first place. Because how else am I going to know how to stop it from wandering? So the second question that I'm going to answer first is, what causes polarity patch wandering? So in order to answer this question, I needed to do a lot of microscopy. I needed to film the polarity patch wandering around. And it turns out that setting up the special slide in order to film cells in a gradient is really time-consuming. It's actually a real pain in the butt, and I'm not a lazy scientist. I'm a practical one. I wanted to film a lot of cells with a lot of different mutations, so that I could really get at the heart of what causes a polarity patch to wander. And I had this rate limiting step of having to acquire the special microfluidics slide, having to set it up, and that was just painful. So I thought, maybe I could use a simpler system to study polarity patch wandering. So it turns out if you treat cells with uniform pheromone, so I simply squirt pheromone on the slide, now they don't think that there's a mating partner over there or over there, because there's pheromone everywhere. But that's okay, because it turns out they still polarize, they just pick a random direction and go in it. So when I treated cells with non-saturating pheromones, so about the concentration of pheromone that they were seeing when they were in a gradient, you can see that the polarity patch was very dynamic as well. So these are cells when in uniform pheromone, pheromone all over, and yet the polarity patch seems to be wandering around a lot. And in fact, I could use a computer to find the centroid of the patch over time. And so this is an example of some tracks. I'm simply showing you for one cell, so in each color is one different cell, the location of the polarity patch over time. So you can see that it sort of wiggles around, but more importantly, I could use this spatial information to quantify the wandering. So I quantified it using a metric called MSD, mean square displacement. And what you need to know about mean square displacement is that it's simply a measure of how far something has moved from the origin over time. And so I averaged a whole lot of polarity patches from a whole lot of cells in this graph. I'm showing you that in non-saturating uniform pheromone, like the movie I just showed you, there is some wandering of the polarity patch. But I wanted to be sure that it was similar to the amount of wandering of cells treated with a gradient of pheromone. And so I compared the number of wandering and non-saturating uniform pheromone with the polarity patch wandering in a gradient. And it turns out that they're almost identical. Phew! So that gives me the freedom to work with cells in uniform pheromone, where I can just squirt it on a slide, which is much easier. And not have to deal with always setting up the microfluidics chamber. So many of the experiments I'll show you today, I did in uniform pheromone. Alright, let's go back to the question, what causes polarity patch wandering? So I came up with this hypothesis, that wandering is caused by vesicle delivery. And in order to understand this hypothesis, you need to understand a little bit about the dynamics of the polarity patch. So I'm showing you down here, simply a fluorescent image of a cell in pheromone, outlined with the dotted line, and the fluorescence, that's Bem1-GFP. So you can see that there's sort of a patch of proteins. And that's what I'm indicating with this graphic here. There's the plasma membrane and then lots of proteins at the membrane. Now, I don't want you to think of this as a raft of all these proteins that are all stuck together, because that's not at all what it's like. In fact, there's two important things going on here. One is that all of these proteins in the patch are actually moving around on the plane of the membrane. None of them are in the membrane, none of them are stuck in the membrane like integral membrane proteins, they're all peripheral membrane proteins. So they're sticky on the surface of the membrane, and they're all sliding past one another. The other thing that I need to point out here is that not every single polarity protein is at the patch. Some of them are down here in the cytoplasm, they're all diffusing around. And importantly, some of them are falling off of the patch, and some of them are actually sticking to the patch or coming on and joining the patch. And an analogy here is if there's a crowd in a park, there's a big crowd all gathered together, so there are some people who are going to come and join the crowd, and there are some people who are like, "Yeah, I'm done here." And they leave the crowd. So the crowd is like the polarity patch, it's this grouping of people that are all sort of milling about, and there are some people who are leaving and there are some who are joining. Okay, so let's get back to the hypothesis, that wandering of the polarity patch, this cluster of proteins is moving around when the cell's trying to find a mate. And I think that it's moving around because of vesicle delivery. So remember, I told you wherever the polarity patch is, that's where the cell is growing. And the reason that the cell is growing there is because there are proteins in the polarity patch that can make actin cables form at that site. So these purple things are actin cables, they're filaments of actin, which is part of the cytoskeleton. And you can think of them sort of like railroad tracks. In that they're used to traffic vesicles. And vesicles are the stuff that the cell needs to actually grow. So in order to grow, it needs to add new cell material, right? And the vesicles are little sacs with membrane on the outside and cell wall material on the inside. So that when a vesicle -- so there's one more thing that's important here, and that is that the vesicle is trafficked, it's literally carried along the actin cable with a motor protein, so that's the little sticks I'm indicating here. And this motor protein actually hangs on to the vesicle on end and actually walks along the filament. And it walks along the filament towards the polarity patch, and it delivers the vesicle at the plasma membrane. And when that vesicle gets to the plasma membrane, it fuses at the membrane, okay? So it's going to fuse at the membrane, and add just a little bit of new membrane. Now, it's important that the polarity proteins which associate with the plasma membrane, they are not associated with the vesicle membrane. So when this vesicle adds to the plasma membrane, it's basically adding naked membrane. So there's this sort of open space, just transiently, for a very short amount of time. Because of course, remember, all these proteins are just sliding around. So some of these proteins are going to slide into that open space. But remember also, that there are proteins that are falling off and coming back on. The people who are joining the crowd and coming away from the crowd. And you can imagine that there's a big crowd in a park, you know there's sort of an empty space on one side, you're less likely to go to that empty space. And the same is true for these proteins. That when they come back on from the cytoplasm onto the polarity patch, they're much more likely to come on where there already are some proteins. And so in this example, when new proteins get added, in the second right after the vesicle got added, the new proteins are more likely to be added here, closer to where there are a lot of proteins than over here, where there are fewer proteins. So there's going to be more added off-center. Now imagine that you're looking down at the crowd, new people get added a little bit off-center from where the center of the crowd was before. And so now the crowd has shifted over a little bit. Now it's not like all of the people in the crowd have moved over, right? It's just that some new members have been added a little bit off-center. Now, when a cell is doing gradient tracking and reaching out to get its mating partner, it's adding a lot of vesicles so that it can grow to meet its mating partner. Which means that one little vesicle probably isn't going to have much effect, but lots of vesicles being added might be enough to cause the polarity patch, the centroid of it, to shift around. Which would look like movement to us when we look down the microscope. So that's the hypothesis that wandering is caused by vesicle delivery. So the way that I'm going to test it is by using a drug called Latrunculin to depolymerize the actin cytoskeleton. So I'm basically going to remove the railroad tracks, so when I treat the cells with latrunculin, the vesicles are still present, and in fact they can still fuse with the membrane, but they're no longer being targeted to the site with the polarity proteins. So if vesicle delivery is causing the polarity patch to wander, then when I treat the cells with latrunculin, I would expect to see a decrease in the amount of wandering. Whereas, if vesicle delivery had no effect, then I'd expect to see no effect. Now before I show you the data, I should mention that I did this experiment in a mutant that has even more wandering than the cells treated with uniform pheromone I showed you before. And I don't have time to explain what that mutant is or why the cells have more wandering, but the reason that I used that strain is because the polarity patch wanders around so much that it allows me to look for small differences in the amount of wandering, which would be harder to see if it didn't wander as much. So in that mutant, I treated it with latrunculin and I saw a decrease in the amount of wandering relative to DMSO, which is the liquid that I applied the drug with. So that was pretty convincing that, or at least it's consistent, with the hypothesis that it's vesicles being added that causes the polarity patch to wander around. But the problem is when you treat cells with a drug, you might have pleiotropic effects, which means you might be affecting lots of things that you don't know what they are. And so, maybe the drug is affecting something else, and that's causing the polarity patch to not wander, as opposed to it affecting vesicles. So I wanted another way to specifically affect vesicle delivery without having to use this drug. So I used instead, a mutation to stop vesicle delivery. Now remember I told you the reason that vesicles traffic along the actin cables is that there's a protein, this with the little legs here, that the motor that hangs on the vesicle on one side and walks along the filament, so that motor protein, I used a mutation in it. A temperature sensitive mutation, so when I put the cells at a high temperature, the motor protein no longer functions. So now, the actin filaments are still present but the vesicles are no longer being delivered along the actin filaments to the polarity site. And again, when I did this in cells with lots of wandering, the high wandering mutant, we saw at high temperatures that cells with this temperature sensitive mutation had less wandering than the wild type control at the same temperature. So together, these data helped convince us that vesicle delivery contributes to the wandering that we see in cells that are trying to sense the gradient. So wandering is caused by vesicle delivery. Good. We've answered question #2 so we can return back to question #1, how do yeast cells orient growth up gradient? Like I told you before, I hypothesized that it's the polarity patch that's doing a biased random walk. The polarity patch is sensing what's the concentration over here and over here and over here and over here, and letting itself be biased by the concentration of pheromone. And if that's right, then polarity patch wandering should be necessary for gradient tracking. So what I want to do is stop polarity patch wandering. And I mentioned that in the beginning, I'm a geneticist. So if I were to stop polarity patch wandering, then I should somehow be able to prevent the cell from being able to orient to the gradient. Now I've told you already two different ways that I can impair the wandering, I can treat the cells with a drug or I can use a temperature sensitive mutation. But both of these ways inhibit vesicle delivery, and what I want to do is I want to stop polarity patch wandering, but allow vesicle delivery so that the cells can grow. Because if the cells aren't growing, how do I know which direction they're trying to go in? So my goal is to somehow find a way to stop the polarity patch from wandering around without stopping vesicle delivery so that the cells are still able to grow and I can tell in which direction they're trying to go. So when I thought about what it is that causes the polarity patch to wander, I realized that it's the fact that the vesicles are naked, right? So when a vesicle gets added to the plasma membrane, it adds this hole, right? This short-term space and all of the proteins that are going to be added to the polarity patch get added to the side where there isn't a hole. So what if there wasn't a hole each time a vesicle got added? So I thought, okay, I'll make the vesicles not be naked. What if I forced a polarity protein to be on the vesicle? So I did that by fusing a protein that normally localizes to vesicles, Snc2, to a polarity protein, Bem1. So polarity protein, Bem1, normally localizes to a polarity patch. And that means that because that fusion protein localizes to vesicles now, because of the fusion to Snc2, that when a vesicle gets added to the polarity site, now there's not a naked open space, it's a space filled with Bem1, which is a polarity protein. And so when new proteins get added, they'll get added all over instead of avoiding that open space. So here's the evidence that this fusion protein actually does reduce wandering. Again I'm using the high wandering mutant strain, and when the cells have wild type Bem1 in them, there's a lot of wandering that happens. But when the cells have the fusion protein, there's basically no wandering. And the amount of wandering that you can see here, this is actually equivalent to the amount of growth that's happening. So the polarity patch is moving only in so much as there's new cell wall material and the cell is growing out. So this fusion protein really blocks polarity patch wandering, but it doesn't stop vesicle delivery. And so these cells can still form a projection and I can then measure what direction they're trying to go in. So going back to my question. How do yeast cells orient growth up gradient? Well, I think the polarity patch wandering is important and so I'm going to stop polarity patch wandering with my fusion protein. And I predict that if polarity patch wandering is important, then by stopping the wandering, I would expect the cells would be bad at doing orientation. They'll pick a direction and go in it, even if it's not the right direction. But if polarity patch wandering is inconsequential, if it has nothing to do with orientation, then it my cells with the fusion protein where the polarity patch doesn't wander at all, they'll be fine. They'll still be able to go up gradient. And be able to find a mate. So before I show you the data of cells with the fusion protein, let me remind you what wild type cells look like in a gradient. So this is a movie I showed you in the beginning, remember there's pheromone being applied from the top. So all of the cells think there's the big sexy alpha cell at the top of the screen. And they're all really good at orienting their growth up gradient. And the cells that don't are able to reorient. But when I looked at the cells that had the fusion protein, Bem1-Snc2, so these cells don't have any polarity patch wandering. So they're again treated with a gradient of pheromone in the special slide, the microfluidics device. What I saw is that there are a lot of cells that go in the wrong direction. And when they go in the wrong direction, they keep going in the wrong direction, they don't reorient. And that led us to believe -- to conclude that the polarity patch wandering actually is important for the cells being able to orient in a gradient and find a mate. So in summary, what I've told you is that polarity patch wandering is necessary for gradient tracking. I think that it's an example of a biased random walk on the inside of a cell, as opposed to the whole cell doing the biased random walk. The other thing, which we weren't expecting to find is that the polarity patch is wandering around because of vesicle trafficking. And that actually is really important, because as a basic cell biologist, I set out to answer one question, how do yeast do gradient tracking? And as a byproduct of what I was studying, I discovered this phenomenon where vesicles cause the polarity patch to be disrupted and cause it to wander around. And that actually has implications for human health possibly. So this is a picture of Candida albicans, which is the type of fungus that causes a yeast infection. And when Candida albicans is in the human host, it makes these long projections that are called hyphae. And they look a little bit like yeast cells trying to mate. And in fact, we know that they grow in a very similar way. They grow just from the tip of the hyphae, just like yeast cells grow just from the tip of the mating projection. And they use a similar set of proteins, polarity proteins. And in fact, they're adding vesicles at the polarity site just like mating yeast cells do. And so it would seem like they might have a problem, because shouldn't the adding of the vesicles cause the polarity patch to wander around? We don't think that these cells are doing gradient tracking when they're growing, they're just growing out. So isn't it a problem that the vesicles should be pushing around the polarity patch? And it doesn't seem to be a problem. So if we were able to understand how these cells are able to overcome the problem of vesicle delivery not pushing the polarity site around, then possibly you can imagine a scenario in which we could harness that information to prevent these cells from being able to make hyphae when they're in humans. And therefore be able to treat some diseases. It's fairly speculative, but you can see how a basic science question led us to some interesting results that have implications in fields beyond what we were anticipating. So with that, I need to thank some important people. First, my PhD advisor, Danny, who was incredibly supportive throughout my PhD. Some other important people that helped me with this project, Trevin and Natasha and Allie, all worked with me in Danny's lab, various parts of the project. I also need to thank our collaborators at UNC Chapel Hill, who did some important computer modeling and provided the specialized microfluidics device for us. And finally, I want to thank Sam and Gao, who helped with the microscopy that I did. And you'll notice that I did a lot of microscopy, so they were very helpful in that regard, as well. And with that, I thank you for your attention.
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Channel: iBiology
Views: 24,910
Rating: 4.9521675 out of 5
Keywords: yeast, G protein biophysics, cell biology, vesicles, iBiology, Cell (Anatomical Structure)
Id: oZWEWbvlVdE
Channel Id: undefined
Length: 34min 56sec (2096 seconds)
Published: Mon Oct 12 2015
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