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Feb 2, 2014

Bonnie Bassler: How bacteria "talk"

Transcript of TED talk

I know you guys think of yourself as humans, and this is sort of how I think of you. This man is supposed to represent a generic human being, and all of the circles in that man are all of the cells that make up your body. There is about a trillion human cells that make each one of us who we are and able to do all the things that we do, but you have 10 trillion bacterial cells in you or on you at any moment in your life. So, 10 times more bacterial cells than human cells on a human being. And of course it's the DNA that counts, so here's all the A, T, Gs and Cs that make up your genetic code, and give you all your charming characteristics. You have about 30,000 genes. Well it turns out you have 100 times more bacterial genes playing a role in you or on you all of your life. At the best, you're 10 percent human, but more likely about one percent human, depending on which of these metrics you like. I know you think of yourself as human beings, but I think of you as 90 or 99 percent bacterial.
The reason that Vibrio fischeri is doing that comes from the biology. Again, another plug for the animals in the ocean, Vibrio fischeri lives in this squid. What you are looking at is the Hawaiian Bobtail Squid, and it's been turned on its back, and what I hope you can see are these two glowing lobes and these house the Vibrio fischeri cells, they live in there, at high cell number that molecule is there, and they're making light. The reason the squid is willing to put up with these shenanigans is because it wants that light. The way that this symbiosis works is that this little squid lives just off the coast of Hawaii, just in sort of shallow knee-deep water. The squid is nocturnal, so during the day it buries itself in the sand and sleeps,but then at night it has to come out to hunt. On bright nights when there is lots of starlight or moonlight that light can penetrate the depth of the water the squid lives in, since it's just in those couple feet of water. What the squid has developed is a shutter that can open and close over this specialized light organ housing the bacteria. Then it has detectors on its back so it can sense how much starlight or moonlight is hitting its back. And it opens and closes the shutter so the amount of light coming out of the bottom -- which is made by the bacterium -- exactly matches how much light hits the squid's back, so the squid doesn't make a shadow. It actually uses the light from the bacteria to counter-illuminate itself in an anti-predation device so predators can't see its shadow, calculate its trajectory, and eat it.This is like the stealth bomber of the ocean.
First we figured out how this bacterium does this, but then we brought the tools of molecular biology to this to figure out really what's the mechanism. And what we found -- so this is now supposed to be, again, my bacterial cell -- is that Vibrio fischeri has a protein -- that's the red box -- it's an enzyme that makes that little hormone molecule, the red triangle. And then as the cells grow, they're all releasing that molecule into the environment, so there's lots of molecule there. And the bacteria also have a receptor on their cell surface that fits like a lock and key with that molecule. These are just like the receptors on the surfaces of your cells. When the molecule increases to a certain amount -- which says something about the number of cells -- it locks down into that receptor and information comes into the cells that tells the cells to turn on this collective behavior of making light.
We also then went to look at what are these molecules -- these were the red triangles on my slides before. This is the Vibrio fischeri molecule. This is the word that it talks with. So then we started to look at other bacteria, and these are just a smattering of the molecules that we've discovered. What I hope you can see is that the molecules are related. The left-hand part of the molecule is identical in every single species of bacteria. But the right-hand part of the molecule is a little bit different in every single species. What that does is to confer exquisite species specificities to these languages. Each molecule fits into its partner receptor and no other. So these are private, secret conversations. These conversations are for intraspecies communication. Each bacteria uses a particular molecule that's its language that allows it to count its own siblings.
Once we got that far we thought we were starting to understand that bacteria have these social behaviors. But what we were really thinking about is that most of the time bacteria don't live by themselves, they live in incredible mixtures, with hundreds or thousands of other species of bacteria. And that's depicted on this slide. This is your skin. So this is just a picture -- a micrograph of your skin. Anywhere on your body, it looks pretty much like this, and what I hope you can see is that there's all kinds of bacteria there. And so we started to think if this really is about communication in bacteria, and it's about counting your neighbors, it's not enough to be able to only talk within your species. There has to be a way to take a census of the rest of the bacteria in the population.
So we went back to molecular biology and started studying different bacteria, and what we've found now is that in fact, bacteria are multilingual. They all have a species-specific system -- they have a molecule that says "me." But then, running in parallel to that is a second system that we've discovered, that's generic. So, they have a second enzyme that makes a second signal and it has its own receptor, and this molecule is the trade language of bacteria. It's used by all different bacteria and it's the language of interspecies communication. What happens is that bacteria are able to count how many of me and how many of you. They take that information inside, and they decide what tasks to carry outdepending on who's in the minority and who's in the majority of any given population.
To finish I'll just show you the strategy. In this one I'm just using the interspecies molecule,but the logic is exactly the same. What you know is that when that bacterium gets into the animal, in this case, a mouse, it doesn't initiate virulence right away. It gets in, it starts growing, it starts secreting its quorum sensing molecules. It recognizes when it has enough bacteria that now they're going to launch their attack, and the animal dies. What we've been able to do is to give these virulent infections, but we give them in conjunction with our anti-quorum sensing molecules -- so these are molecules that look kind of like the real thing, but they're a little bit different which I've depicted on this slide. What we now know is that if we treat the animal with a pathogenic bacterium -- a multi-drug-resistant pathogenic bacterium -- in the same time we give our anti-quorum sensing molecule, in fact, the animal lives.
What I would hope that I could further argue to you is that this is the invention of multicellularity. Bacteria have been on the Earth for billions of years; humans, couple hundred thousand. We think bacteria made the rules for how multicellular organization works. We think, by studying bacteria, we're going to be able to have insight about multicellularity in the human body. We know that the principles and the rules, if we can figure them out in these sort of primitive organisms, the hope is that they will be applied to other human diseases and human behaviors as well. I hope that what you've learned is that bacteria can distinguish self from other. By using these two molecules they can say "me" and they can say "you." Again of course that's what we do, both in a molecular way, and also in an outward way, but I think about the molecular stuff.
Finally, I wanted to show you this is my gang at Princeton, New Jersey. Everything I told you about was discovered by someone in that picture. I hope when you learn things, like about how the natural world works -- I just want to say that whenever you read something in the newspaper or you get to hear some talk about something ridiculous in the natural worldit was done by a child. Science is done by that demographic. All of those people are between 20 and 30 years old, and they are the engine that drives scientific discovery in this country. It's a really lucky demographic to work with. I keep getting older and older and they're always the same age, and it's just a crazy delightful job. I want to thank you for inviting me here. It's a big treat for me to get to come to this conference.
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Anuj in Himalayas

Hi i am connecting disqus with my blog for healthy interaction and open dialogue