Hello. My name is Dominique Bergman, and I'm a professor at Stanford University, as well as a number of other things. I'm an investigator at the Howard Hughes Medical Institute and affiliated with the Carnegie Institution and their Department of Plant Biology. And those are all wonderful institutions to be a part of, particularly because I can tell you about some of the work that's going on in all of those fields and also in our group, having to do with plants and having to do with how plants and their importance for us as human beings. So, I'm going to divide this into three different sections.
I'll begin with a broad overview, telling you about some of the key issues in plant development. So, why are plants important? What can we learn from them?
Why should we care about how they develop? And then I'll... in doing that, tell you a little bit about specific cells in plants, cells that are called stomata that are really important. They're important for getting the atmosphere, the carbon dioxide from the atmosphere, into the biosphere, into living things.
And that's useful because we eventually want to eat those things. So, I'll tell you about stomata, their function, but also how we use them as a model for stem cells. So, that'll be a more specialized topic that I'll continue in part two. And then in part three, come back to this idea of how plants and the environment are interacting and the effect of that on humankind. So, one of the things that I think is really important, and kind of obvious but we don't always think about it, is that we're completely surrounded by plants.
So, I'm at Stanford, normally during the day. I'm up here at UCSF filming this. And on the way, I take the train, and you see plants all around. You can see plants in urban settings.
So, this is actually the San Francisco Botanical Garden. You can see wonderful trees and grass and a few people in there. But it's really dominated by plants.
And so, if you walk through the woods, it's an environment that's dominated by plants. They're surrounding us everywhere. They've been there before us. So, this is actually a modern forest, but it's... It's illustrating probably what life looked like before we were on the planet.
So, plants covered all the surfaces. They were up in the air. They were down... mosses down on the ground.
And they really were important because without plants we wouldn't have oxygen in the atmosphere. And so plant... so animals aren't actually able to live without that. Today, we do have environments like this, but we also have marginal environments. Ones where it's very difficult for humans to live in.
But plants can do just fine. So, this is actually Craters of the Moon up in Idaho, and you can see just in that distance that there are a few trees that have just managed to make it out there, but it's a very, very harsh environment. It's very dry. Humans are not so happy to be there. These are my nieces that are complaining a lot.
So, plants can live in places without us. They can live in harsh environments. And it'd be nice to know, how is it that they do that? How are they able to survive in a climate that may be changing? So...
One of my colleagues, Elliot Meyerowitz, who's down at Caltech a number of years ago, called plants the ultimate outgrew. So, what does he mean by that? So, often in biology we're interested in comparing things. So, why is one thing like another? If two things started out very differently but then ended up the same, there might be some common principle there.
So, if you look in evolution, plants and animals are two very successful families. But it's been a long time since they had a common ancestor. So, this is a diagram that's actually not... So, this is not that accurate, but accurate enough for my purposes, and it's a cute cartoon. And what you can see is, at the bottom...
so, plants and animals up at the top, you can see some humans, some fish, some plants... they're very different from one another now, but they came from a common ancestor, and that common ancestor actually was a single-celled organism. Everything since that was done separately.
So, the last time that humans and plants, or monkeys and plants, snails and plants shared something in common, it was when there was only a single cell. So, they do different things, they've had different strategies in life. It's interesting to know what those strategies are, but sometimes, and to me this is really fascinating, even though they are so different, sometimes they come up with exactly the same solution to a problem that they have to face. And that tells us something that all organisms are going to solve it in the same way.
Okay, so let's look at the top of this tree. So, we've got some examples, some humans and some plants. So, what's the same and what's different? What are the key features that we need to focus on?
Well, I'm gonna talk about development. And so, I need to back up and tell you what I mean by development. And so, development is the process by going... by which you go from a single fertilized egg into something wonderful and complex, like a human being. and all of the different things that happen.
So, that cell needs to divide into many different types of cells. Those cells need to move around if you're an animal. You need to form the shape that is a human body, so two arms, two legs, a head, and all those different parts.
So, developmental biology is that process by which you get all of that complexity. So, whether you're a plant, and I'll show plants in green mostly and animals in beige or red, you start out the same. So, you start out with a fertilized egg. And then you go through some development and form some things, some limbs.
So, if you're a baby, you've got a head and a couple of arms and legs. If you're a plant, you start making leaves and roots. And so, this is pretty much what you end up with, just coming out of... this is birth, essentially.
So, a germinating seedling, one that's just come out of the seed and into the light, or an infant. So, then you go through the process of developing into a mature adult. So, if you're a plant, you start to make flowers and more complex things. If you're an adult, you get bigger. And then it's time to reproduce.
That's an important thing for both plants and animals to do. If you're a plant, often you're self-fertile. Humans need a little bit of help, so we need a man and a woman here. And then you can produce some offspring, and we repeat the cycle.
Okay? So, that's something that both of these types of organisms need to solve. But there are some differences between plants and animals.
if you hadn't noticed that before. And some of the key differences between plants and animals have to do with food. So, plants are our primary producers.
They take basic elements from the soil, and sunlight and sun energy, carbon dioxide from the air, and from that they generate carbohydrates and all the building blocks of life. So, without plants, we wouldn't be around again. There are some exceptions. that will consume animals, like a venous fly trap that will trap flies.
But other than that, most of the time the plants are producing food and the animals are consuming food. And in terms of developmental biology, what's important about that is plants have ways of capturing sunlight and think... nutrients from the soil, whereas animals are specialized to have digestive systems so that they can consume things that way.
Another thing that's very different between plants and animals is mobility. So, plants are rooted where they are. They are not going to move throughout their lifetime. And animals, of course, can run around, they can move to New Jersey if they want to. They're a very different type of organism.
And that also leads to different strategies with development. So, if you're a plant and you know you can't move, you just have to face whatever you're going to see. So, you might have more sunlight sometimes and less sunlight, and that's going to change your development. Whereas an animal is going to try to move... to a more optimal place.
So, there's mobility, and that's what the whole organism does. There's also motility, and that... sometimes we term that in terms of cells, so motility would also be movement, but here I'm not talking about what the whole organism does, I'm talking about what constituent parts do. So, what's really key here...
and again, I'm showing plant cells in green and animal cells in red... Plant cells are... are in boxes, they've got walls around them, so whatever they're born next to, they're next to for the rest of their life.
And these cells can divide, and the plant will grow, but the cells never move relative to one another. Animal cells are really different. So, animal cells can move around, here's my little animation of cells moving around, and you can imagine cells in your bloodstream are obviously moving around, but cells during development move around.
So, if you're a ball of cells, and that's how most organisms start out, If you want to become a long, skinny thing, if you're an animal, those cells can move so that you get a long, skinny thing. Whereas in plants, they have to divide in a particular direction to generate the same thing. So, those are slightly different strategies. Alright, so let's come back to this idea of development in plants and animals. And I'm gonna show you some real plants and animals developing, rather than just some clip art.
So, here's two examples. And these... this also brings up another point, that... Often, when we're interested in human health and disease, we're really focused on humans, but we can't do all the experiments on humans. And so we use a set of model organisms that have aspects of development that are useful and helpful for us to understand ourselves.
Same thing with plants. So, things like wheat and corn are incredibly important as food stocks, but they're difficult to work with. They're big, they take a long time to grow. And genetically, there are some difficulties. And so often we use a model for those, and the model that we use, shown here, is a model called Arabidopsis.
Arabidopsis is a little plant, it's related to broccoli, it grows about that tall, and has a number of advantage... nice advantages for growing in the lab. Okay, so whether we're looking at an animal or a plant model that's developing, they go through the same kind of processes.
So, if you're a plant, you start out as an embryo. And these are a wonderful set of images by my colleague, Stuart Gilmore. And Stuart looked at the embryo.
It's actually inside of a seed in the beginning. But it starts out a bit like a ball of cells. And it grows. And it starts to create these two leaves, embryonic leaves, at the top.
That's as far as it gets there. And when it's a seed... The end of its embryonic life is very simple. It has two leaves at the top and a single root at the bottom.
Then, throughout its post-embryonic life, so after it's been born, then it gets much more complex. And that's a bit different than animals. So, in animals...
and here's an example of a zebrafish. So, in the very beginning, it's quite similar. So, you have cells that divide and they make a ball of cells. But then, if you look at it through its embryo...
By the time it kind of hatches as a larvae, you can see that it already looks like a fish. It's got a head and a tail. It has all the organs. You can see its eye.
You can see some stripes down the side. And the difference between an infant or a just hatched fish and the adult is it's not quite so great. It's made all of the limbs that it's going to make. It's not going to grow any more eyes.
It's not going to grow any extra organs. And that's a big contrast to a plant. which is constantly generating new organs.
So, this kind of development actually impacts a lot on how plants and animals can do things differently. And so this is, I think, a nice example of humans and their offspring, and plants and their offspring, and their development. And if you think about human development, the really key parts of human development, when you're generating all of the organs and... and all of the, really, form of a human baby, all of that's happening in utero, in a very controlled environment. So, mom's womb has all the nutrients you might possibly want, it's constant temperature, lots of things are buffered, and so that organism is in a very, very constant environment.
And so, Eva, here, was inside of my sister, generating her beautiful blue eyes and her arms and her legs. without actually having to deal with the environment. Now, these plants that are in front of Ava, they were born... when they came out of their seed, outside of their mother, they only had two leaves.
And yet you can see that they now have a whole lot of leaves and a whole lot of other things. All of that development was done in response to the environment. They were out there, they were dealing with how dry it was in some years, or how wet it was in other years, how much sunlight there was, whether or not there were insects that were trying to eat them.
And so, lots of things about that development is really, really different. And so, plants, over the time that they've been around, because of that strategy, because they're constantly having to deal with the outside world, that has some implications for how... how they develop. And it turns out that some of those...
here's the punchline... they have... they're very good at regenerating.
They get eaten a lot, and so they can regenerate parts. We're not so good at that. If our arm gets chopped off by a crocodile...
We don't really have an opportunity to grow a new one. But plants are constantly able to do that. If the environment changes, we have pretty limited abilities to respond to that. I mean, obviously diet and exercise can make someone larger or smaller. But plants can be a hundred times bigger in some environments than in others.
And so you can see that actually, that extreme flexibility, you can see as an example in these maple trees. So, on one side we have a maple tree that's been part of a bonsai. So, this is in a very constrained environment. There's not too many nutrients sitting there in that dish. There's not a whole lot of light in someone's living room.
So, that's fairly limited in how big that can get. So, not only is it not very tall, but all the leaves are smaller. If this was a fruit tree, you'd have tiny little fruits as well. Put that in contrast to...
this is a picture from a garden in Kyoto, and here's another maple tree. Genetically, very, very similar, but it's much, much bigger. And this particular tree, you can see it growing next to some other trees.
It's going to grow out in a particular direction to reach the sun. So, if plants can be flexible in their development and form all sorts of different organs at different times, how do they actually do that? And to do... to understand that, you need to look at the different parts of the plant that actually generates the... generates all of those organs.
And so, the important parts of the plant, there are things called meristems. So, meristems are like stem cell populations, and I'll tell you a bit more about it in a few slides. So, there are two really key meristems.
So, they're formed in the embryo. So, an embryo about this old, that has these two cotyledons sticking up, two embryonic leaves, and a root, will have a stem cell population at the center called the shoot apical meristem. So, it's apical, meaning it's at the tip, and shoot because it's generating all of the organs of the shoot, so the leaves and the branches and the flowers. At the bottom of this embryo, equally important, is the root apical meristem.
And the root apical meristem is going to generate all of the root organs as the plant lives. And so, this is them in the embryo. If you look at them much later on, if you think about a plant, this is an example of a number of plants that would be growing in a field.
And in these plants, what you can see is above ground, there's what we normally see, those plants that have different forms and different types of flowers and leaves. And those are all generated by the activity of the shoot meristem. But something that's usually hidden to us is the roots underground.
And you can see here just how big those roots are, how complex they are, how many different forms they take, and how big... they actually can be larger in total size than what's actually above ground. Okay, so one of the important key words for these meristems is that they're pluripotent.
They're actually able to generate lots of different types of tissues. So, if you take something like a root... A root, if you look at the different tissue types in there, it actually makes hairs to go out and collect nutrients.
It has... in the center of it, it has a vascular system that takes those nutrients and carries them up to the top. In the...
in the leaves, in the shoot, you have cells that are specialized for take... for photosynthesis, other cells that are specialized for transport or defense or other things. So they're pluripotent in that they're able to make lots of different cell types and lots of different organ types. Now...
Well, I always like to see development in action, and so this is giving you an idea of the beginning and the end point, but what's really fun is to be able to actually watch development as it unfolds. So, this is a movie that was taken... this is a set of images done by Nick Kaplinsky at Swarthmore College, and what he did was simply take a camera and set it up over developing a Arabidopsis seedling. And he did this for about a month, and what we're gonna see is this little seedling in the center is gonna go from... having only four leaves into a mature plant that's actually going to generate a flower.
So, if we watch this, we start to see it grow. So, those leaves get bigger, they start to expand, but then new leaves come out. And those new leaves are coming out of the center of it because of that shoot apical meristem. So, that meristem is active, it's generating new leaves that come out. And what you'll also notice is that the leaves come out in a spiral.
So, what you'll see is they fill in the gaps. And that's important because plants are photosynthetic, so they're trying to capture the light. And by doing this, they're able to space the leaves out so none of them are sitting right on top of each other and blocking the light. So, this will continue for a while, and at the very end it becomes reproductive, so it's actually generating... in the very center of there, there's actually a flower that's gonna open up a little bit out of the frame of this movie.
So, that's development, and that's all because of how that shoot apical meristem is acting. Alright, so stem cells at the meristems are very powerful, they're very long-lived, they make lots of different cell types. There are some more limited stem cell types.
These are called meristemoids, so oids for smaller version of a meristem. And these can't make the entire plant, and they're more limited, but they make very important cell types. And actually, we're, in my group, very excited about these because this is really the subject of our work. So, if we were to look at this plant and not focus so much on the shoot and the root anymore, but just look at one organ, the leaf, there are meristemoids, other populations, that are going to help generate that leaf.
So, these cells will divide, and they'll end up generating all of the cell types that make up the epidermis of the leaf. And there are two very important cell types that I'll... that I'll talk about that come from this lineage. A plant has to be waterproof. It has to be watertight.
And so it's got cells that interdigitate, and those are these pavement cells. Here you can see they look like jigsaw puzzle pieces. And they form a watertight seal between the plant and the... and the atmosphere. That's great.
It keeps the... the plant protected. But plants actually have to interact with the atmosphere. They actually need to be able to take in carbon dioxide from the atmosphere into the plant.
And they need to release water out and oxygen out to the atmosphere. And if you're completely... tightly sealed off like that, it doesn't really work. So, in between these sealed off areas are things called stomata. And stomata are really my favorite cells on the planet.
Stomata are actually structures that consist of two cells. They're identical cells, and they form a valve. So, these cells open and close, and that valve is how oxygen comes out of the plant, carbon dioxide goes into the plant. So, these two cells are really, really critical. The pore in the center of them is also critical.
And underneath them, this is just the surface of the plant, if you looked underneath, there would be cells designed to capture carbon dioxide as it comes in. Okay. So, I've been mentioning, as I talk about meristems and meristemoid cells, that can generate whole organs.
And they're related to stem cells that we think about in terms of animals. So, stem cell populations in animals, they've become very famous in the news recently, but we also think about them in terms of our normal development. There are ways of regenerating our cells. If you have a wound, you can heal that wound.
If you exercise a lot, muscle stem cells can generate larger muscles. So, what I think is actually very key is to think about plants and animals and think about their stem cell populations and how they work. So, I've introduced the plant ones.
I'll give you a key. So, we're going to look at a few key features of animal stem cells so that we can compare those. So, at the heart of stem cell divisions are things called asymmetric cell divisions.
So, as a cell divides, it's going to create two daughter cells. And there are lots of mechanisms during division to make sure that those two daughter cells both inherit the same DNA and certain things that they both have to have. So, it's important to make these two daughter cells different from each other sometimes. So, in an asymmetric stem cell division, you have a mother cell that divides into two daughter cells, and those two daughter cells are different from one another.
When they're stem cells, one of those cells, in this case this one, acts just like its mother, so it replaces the mother. The other cell goes off and does something different. And so, because of this pathway, if you have a mother cell that recreates itself and then generates something different, then you always keep a stem cell, you always keep something there that's ready to regenerate. Okay.
So, that's going to be true for whether you're a plant or an animal. When we talk about stem cells in animals, we talk... I'll go through several different things, the ones that are naturally in our body, and then some more recent work in which scientists have been able to reintroduce... to generate stem cells from cells that had already been something else.
So... So, if you are looking at an embryo, a human embryo or another mammal... again, we're gonna go back to fertilized egg...
so, eggs then divide a number of times. Here, they often divide symmetrically at the beginning, so all the cells are identical, but then they start to divide a bit more and divide asymmetrically, and cells start to do different things. So, there's a stage called the blastocyst stage, where there's just a few cells that are kind of clumped on one side of the embryo. At that point... And every one of those cells has the potential to become any other cell.
So, when people make embryonic stem cells, when those are derived, this is the stage from which they're derived. So, those cells are pluripotent or totipotent, they're able to make everything. Then there's special signals that happen normally during development that make them do certain things to make this cell...
even though it could make anything, make this cell make blood, this cell make muscle, this cell make liver, for example. Alright. So...
That would be the early part of development. Then these cells start to organize themselves, so they move around and start forming the different parts of the animal. And so, if we were to follow that a little bit later, then we get on to something that looks a bit more like a human, something that has limbs and internal organs.
And that's at a stage where, in those internal organs, or in something like the skin, those are specific cells. And very much like the meristemoids that I talked about that only make a few different things, these are adult stem cells and they only make a few things. So, adult skin stem cells will only make skin. They're not going to regenerate muscle or bone.
And so this is something that they're made in the embryo, but they persist throughout the adult, and they're important for regeneration, wound healing, and growth. And just to give you a quick example of some of the somatic or adult stem cells, those are found through many different tissues in our body. So, things that regenerate a lot, things like the skin and the muscles and the blood. Brain is still a little bit debatable, but there is some idea that you can regenerate neurons. Alright, so that was a little bit of a trip through some of the important things about stem cells in humans, but I started off with plants.
So here's the big question. If we want to know how these adorable humans are made and how they maintain themselves and how they become adults and resistant to injury and all of those wonderful things... What is it that we can learn from plants?
Why would we study plants instead of another animal? And I want to bring up a couple of things. I've kind of alluded to the fact that plants, because they live so long, because they constantly regenerate new organs and regenerate themselves, they're really good at it.
And so we ought to figure out how they've done it to figure out how we do it. The other thing that becomes an issue when you think about stem cells is we often talk about a balance. Stem cells are things that keep renewing. But there's a danger to that.
If a cell renews itself over and over and over again, that's getting to be a tumor. So, a tumor is something that divides and keeps dividing out of control. And so, in animals, we often think about that balance. How is it that you can regenerate enough times but not overshoot? And plants, we don't know how they've done it, but they've done a really remarkable job of not getting cancer and yet being able to regenerate themselves for hundreds of years.
And so, what can we learn from them? So, I'm gonna give you a few examples in this and in part two about what we can learn about plants and stem cells. To give you just a few key bits, one of the things that interests our lab a lot is, how does a stem cell get made?
What's... we can think about stem cells as they... as they get reactivated and are working, but what makes a stem cell in the first place? Why is a stem cell a stem cell and not another type of cell?
And that's very difficult to address in animals, particularly mammals. A part of that is because they're inaccessible. So, when stem cells are made, if we look at a 20-week-old fetus, it already has the stem cells established in its muscle and liver and epithelia skin, for example.
But we have no access to that. We have no access to that in humans, even if we look at something like mouse. which experimentally we have more access to, it's still something happening inside an embryo, inside a mother.
So it's very difficult. We can't stick a microscope in there very easily to see what's going on. Plants, on the other hand, they're continuously making stem cells, and they're continuously renewing them, and they're out there for us to see.
So, when we look at a plant like this, it is constantly making stem cells. Every time it makes a branch, it makes a new population of stem cells. Every time it makes a flower, They're new stem cells for those reproductive organs.
And then in the leaf, as I mentioned before, those meristemoids, those are new stem cell-like populations that are making the leaf. So I think it's important to add plants into a whole set of different organisms that we use to understand stem cells, because nature has solved problems having to do with regeneration and regrowth in many different ways. And we've learned a lot from work in other animals, for example, in planaria, flatworms.
These can be divided up into little bits and pieces, and there's a wonderful iBio seminar on these, where those parts can regrow. The same thing is true for amphibian limbs, so if you can cut off a frog limb or a salamander limb, that will regrow. We can't do that right now, but it'd be really wonderful to figure out how those organisms do that.
And so I'd like to add plants into this group of organisms that we study, because they have certain properties that are very useful. And if you think about that tree of life, and it's going to come up a lot more in part 2 when I start talking about individual genes, what we find is that even though they're quite different in certain ways, underlying the genetic circuits for development are actually quite similar. So, the last part on this slide I have is an embryonic stem cell.
And I wanted to bring up one other thing, which is I've been talking about stem cells naturally, how they normally occur in the body. But a huge, exciting field right now is in what we can manipulate in... as scientists, a little bit outside of nature.
So, the induced pluripotent stem cell. So, these are iPS cells. This is the idea... it was a Nobel Prize-winning discovery a number of years ago, where normally in development you go from a cell that can make anything into a specialized cell, but it was thought that you can't go back. However, this work shows that you actually can go back.
And so it's possible to take something that is a mature cell type, so for example a fibroblast, some part of the skin, put that in a dish, culture it with the right environment and the right additions, and then generate something that becomes, again, a pluripotent stem cell, something that can make other cell types. And then by adding in specific factors, you can direct those... those pluripotent stem cells to become other cell types, like blood cells, or muscle cells, or even nerve cells.
So, the discovery and the work on iPS cells in humans was, of course, very, very exciting. As plant biologists, though, it reminded us of some work that had actually been done about 70 years ago. So, plants...
for a long time, we've known about how to regenerate those, how to actually convert mature cells back into a pluripotent state. And so, work... so, this is actually some examples of doing exactly the same things you would with iPS cells.
You isolate plants. You... you...
So, you take, you know, mature plants that are differentiated, you make them into a pluripotent stem cell in a dish, and then you regenerate them. And what's interesting here is that you're actually regenerating the entire plant, so not just individual cell types that are not very organized, but you actually generate organs that look like leaf organs or organs that look like flowers. So, plants...
plants are very, very good at regenerating back into a whole plant. And I would say that's actually really remarkable. and kind of fun about this is that this, of course, is done in a science environment, in a sterile culture with a lot of high-tech equipment. But the one thing about plants is you may have actually done some of this yourself.
So, this is from a website for moms to do science projects with their kids. And this is an experiment showing that you can actually make your own regenerated stem cell populations in plants simply by cutting off the bottom of a leaf. I'm at a stem here, adding a few things, like maybe some aspirin, putting them in water, and putting them on your windowsill.
And so you then become a stem cell biologist in a few easy steps. Alright, so I want to kind of come to the conclusion of this, and thinking about how plants are useful for us understanding both their own development, which is fascinating, but also reflecting back on our development, and particularly in terms of stem cells. So, the first thing is that... Plants do have stem cells that last throughout their lifetimes, and these lifetimes can be hundreds or thousands of years.
But they're also making new stem cells, so every time they make a new organ as an... as an adult, they're generating a new stem cell population. And because they're doing that, they're accessible. And that's gonna be a big part of... of part two, where I talk about meristemoids in the leaf that we can actually film and we can watch them develop.
We can watch them go forward, we can actually watch them go backward and regenerate. They're very good at regenerating. I've reiterated that point a number of times.
And then finally, what you'll hear in the next part is that this is all wonderful that plants can do this. What does it reflect about for us? One of the interesting things that we found by looking at the genetics underneath this is that the genes that control plant stem cells and plant development are actually very similar to ones that we know from animal development. So we can learn a lot by comparing things at the genetic level. Okay, so that's the end of part one, where I talk about some of the key issues in plant development, particularly related to stem cells.
In part two, I'll move on from there and talk a bit more about the work that we do in our lab, looking at a particular stem cell type in the epidermis, in that limited stem cell. And then in part three, I'll focus on the function of the end product of that stem cell and how that actually affects the global climate. So, this work...
So, this work is done... it's supported by a number of people. It's supported by a wonderful lab group that I have at Stanford University. And in the next slides, you'll hear about specific contributions from different members of the lab. But it's also been funded by a number of sources, and that's absolutely critical for science to keep getting done.
So, we're indebted to the National Institutes of Health and the National Science Foundation for supporting this work. At Stanford, Bio-X is an interdisciplinary program that's allowed us to do some really interesting climate work that you'll hear in part three. And I was recently part of an initiative that brought plant biology into the Howard Hughes Medical Institute, a wonderful collaboration between the Gordon and Betty Moore Foundation and HHMI. And then finally, I need to acknowledge some of the models for some of my slides. Gabrielle, who you can guess is my sister, and Maya and Ava.
two of the small adorable children that you saw.