Bacteria are the oldest living organisms on the earth. They've been here for billions of years, and what they are are single-celled microscopic organisms. So they're one cell and they have this special property that they only have one piece of DNA. So they have very few genes and genetic information to encode all of the traits that they carry out. And the way bacteria make a living is that they consume nutrients from the environment, they grow to twice their size, they cut themselves down in the middle, and one cell becomes two, and so on and so on. They just grow and divide and grow and divide -- so a kind of boring life, except that what I would argue is that you have an amazing interaction with these critters.
Bakterije su najstariji živi organizmi na Zemlji. Postoje ovde milijardama godina, i one su ustvari jednoćelijski mikroskopski organizmi. Znači, one su samo jedna ćelija, i imaju jedno posebno svojstvo, da imaju samo jedan DNK molekul. Imaju veoma malo gena, i genetskog materijala za ispisivanje svih sposobnosti koje nose. A način na koji bakterije žive, jeste taj da one uzimaju hranljive sastojke iz sredine, porastu duplo u odnosu na svoju veličinu, podele se po sredini, i jedna ćelija postaje dve, i tako dalje i tako dalje. One samo rastu i dele se, rastu i dele se - znači prilično dosadan život, osim, što bih htela da vam pokažem, jeste da imate fantastičnu interakciju sa ovim stvorenjima.
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 the cells that make up your body. There's 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. So at the best, you're 10 percent human; 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.
Znam da vi o sebi mislite kao o ljudima, a ovako ja otprilike mislim o vama. Ovaj čovek treba da predstavlja ljudsko biće, generalno, i svi krugovi na tom čoveku su sve ćelije koje čine vaše telo. Postoji otprilike trilion ljudskih ćelija, koje čine svakog od nas, ko smo i šta smo sve sposobni da uradimo, ali postoji 10 triliona bakterijskih ćelija u vama i na vama, u bilo kom trenutku vašeg života. Znači, 10 puta više bakterijskih ćelija nego ljudskih ćelija na jednom ljudskom biću. I naravno, DNK je ono što se računa, pa su tu svi A, T, G i C, koji čine vaš genetski kod i daju vam sve vaše očaravajuće karakteristike. Vi imate otprilike 30.000 gena. E pa, kako izgleda, imate 100 puta više bakterijskih gena, koji igraju neku ulogu u vama ili na vama, tokom čitavog vašeg života. U najboljem slučaju, vi ste 10 procenata čovek, ali verovatnije negde oko jednog procenta čovek, u zavisnosti od toga koja vam se od ovih metrika više dopada. Znam da o sebi razmišljate kao o ljudskim bićima, ali ja o vama razmišljam kao 90 ili 99 procenata bakterija.
(Laughter)
(Smeh)
And these bacteria are not passive riders. These are incredibly important; they keep us alive. They cover us in an invisible body armor that keeps environmental insults out so that we stay healthy. They digest our food, they make our vitamins, they actually educate your immune system to keep bad microbes out. So they do all these amazing things that help us and are vital for keeping us alive, and they never get any press for that. But they get a lot of press because they do a lot of terrible things as well. So there's all kinds of bacteria on the earth that have no business being in you or on you at any time, and if they are, they make you incredibly sick.
Ove bakterije nisu samo pasivni putnici, one su neverovatno važne, one nas održavaju u životu. One nas prekrivaju nevidljivim oklopom koji nas štiti od različitih povreda okoline, kako bismo ostali zdravi. One vare našu hranu, prave naše vitamine, one ustvari uče vaš imuni sistem da loše mikrobe drže napolju. Znači, one rade sve ove neverovatne stvari, koje nam pomažu i koje su neophodne kako bismo živeli, a nikada se ništa o tome ne piše. Ali se mnogo piše o njima, jer one isto tako prave mnoge strašne stvari. Znači, postoje različite vrste bakterija na Zemlji koje nemaju nikakve potrebe da budu u vama ili na vama, u bilo kom momentu, a ako jesu, onda vas čine neverovatno bolesnim.
And so the question for my lab is whether you want to think about all the good things that bacteria do or all the bad things that bacteria do. The question we had is: How could they do anything at all? I mean, they're incredibly small. You have to have a microscope to see one. They live this sort of boring life where they grow and divide, and they've always been considered to be these asocial, reclusive organisms. And so it seemed to us that they're just too small to have an impact on the environment if they simply act as individuals. So we wanted to think if there couldn't be a different way that bacteria live.
I tako je pitanje za moju laboratoriju da li želite da mislite o svim dobrim stvarima koje bakterije rade, ili svim lošim stvarima. Naše pitanje je bilo kako one uopšte mogu bilo šta da urade? Mislim, one su neverovatno male, potreban vam je mikroskop da vidite jednu. Žive taj neki dosadan život, u kom rastu i dele se, i oduvek se smatralo da su asocijalni, usamljeni organizmi. I tako nam se činilo da su isuviše mali da bi imali uticaja na okolinu ako delaju pojedinačno. I hteli smo da razmišljamo o tome da li postoji drugačiji način na koji bakterija živi.
And the clue to this came from another marine bacterium, and it's a bacterium called "Vibrio fischeri." What you're looking at on this slide is just a person from my lab holding a flask of a liquid culture of a bacterium, a harmless, beautiful bacterium that comes from the ocean, named Vibrio fischeri. And this bacterium has the special property that it makes light, so it makes bioluminescence, like fireflies make light. We're not doing anything to the cells here, we just took the picture by turning the lights off in the room, and this is what we see.
Ideja je potekla od jedne morske bakterije, bakterije koja se zove Vibrio fischeri. Ono što vidite na ovom slajdu je samo jedna osoba iz moje laboratorije kako drži bocu sa tečnom kulturom bakterije, bezazlene, prelepe bakterije koja dolazi iz okeana, i zove se Vibrio fischeri. Ova bakterija ima posebnu sposobnost da stvara svetlo, i tako stvara bioluminiscenciju, kao što svici stvaraju svetlost. Mi ovde ništa ne radimo sa ćelijama. Jednostavno smo napravili fotografiju kada smo isključili svetla u prostoriji i ovo je ono što vidimo.
And what's actually interesting to us was not that the bacteria made light but when the bacteria made light. What we noticed is when the bacteria were alone, so when they were in dilute suspension, they made no light. But when they grew to a certain cell number, all the bacteria turned on light simultaneously. So the question that we had is: How can bacteria, these primitive organisms, tell the difference from times when they're alone and times when they're in a community, and then all do something together? And what we figured out is that the way they do that is they talk to each other, and they talk with a chemical language.
Ono što nam je ustvari bilo zanimljivo, nije to da bakterija stvara svetlost, nego kada bakterija stvara svetlost. Ono što smo primetili jeste da kada su bakterije same, kada su bile u razblaženoj suspenziji, one nisu stvarale svetlost. Ali kada se broj ćelija uvećao, do neke određene vrednosti, sve bakterije su simultano uključile svetlo. Pitanje koje smo imali je kako bakterije, ti primitivni organizmi, mogu da uoče razliku između toga kada su same, i kada su u zajednici, i onda sve zajedno urade nešto. Ono što smo shvatili, jeste da je način na koji to rade ustvari razgovor, i da one razgovaraju jezikom hemije. Ovo sada treba da bude moja bakterijska ćelija.
So this is now supposed to be my bacterial cell. When it's alone, it doesn't make any light. But what it does do is to make and secrete small molecules that you can think of like hormones, and these are the red triangles. And when the bacteria are alone, the molecules just float away, and so, no light. But when the bacteria grow and double and they're all participating in making these molecules, the molecule, the extracellular amount of that molecule, increases in proportion to cell number. And when the molecule hits a certain amount that tells the bacteria how many neighbors there are, they recognize that molecule and all of the bacteria turn on light in synchrony. And so that's how bioluminescence works -- they're talking with these chemical words.
Kada je sama, ne pravi nikakvo svetlo. Ali ono što radi je da stvara i luči male molekule, koje možete da zamislite kao hormone, i to su ovi crveni trouglovi, i kada je bakterija sama molekuli samo plutaju okolo i nema svetla. Ali kada bakterija naraste i umnoži se, i kada svi učestvuju u stvaranju ovih molekula, molekul -- vanćelijska količina ovog molekula povećava se proporcionalno broju ćelija. I kada molekuli dođu do određenog broja to govori bakteriji koliko suseda ima, one prepoznaju taj molekul i sve bakterije uključe svetlo, sinhronizovano. Tako funkcioniše bioluminiscencija -- one razgovaraju ovim hemijskim rečima.
The reason 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're looking at is the Hawaiian bobtail squid. It's been turned on its back, and what I hope you can see are these two glowing lobes. These house the Vibrio fischeri cells. They live in there, at high cell number. That molecule is there, and they're making light. And the reason the squid is willing to put up with these shenanigans is because it wants that light.
Razlog zbog kojeg Vibrio fischeri to radi, dolazi iz biologije. Opet, još jedan utikač za životinje u okeanu, Vibrio fischeri živi u ovoj sipi. Ono što vidite je Hawaiian Bobtail sipa, koja je okrenuta na leđa, i ono što se nadam da možete da vidite, su ova krila koja sijaju, i u kojima su smeštene ćelije Vibrio fischeri, one tu žive i kada je visok broj ćelija, taj molekul je prisutan i one stvaraju svetlost. Razlog zbog kojeg sipa prihvata ove podvale je zato što želi to svetlo.
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. And 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. So on bright nights when there's 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 the specialized light organ housing the bacteria. And 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. So it actually uses the light from the bacteria to counter-illuminate itself in an antipredation device, so predators can't see its shadow, calculate its trajectory and eat it. So this is like the stealth bomber of the ocean.
Ova simbioza funkcioniše jer ove male sipe žive uz samu obalu Havaja, u plitkoj vodi, dubine kolena. Sipa je noćno stvorenje, tako da tokom dana spava zakopana u pesku, ali noću, ona mora da izađe kako bi lovila. Tokom vedrih noći, kada ima dosta mesečine i svetlosti zvezda, ta svetlost može da se probije kroz vodu u kojoj sipa živi, pošto se nalazi u plićaku. Ono što je sipa razvila, jeste neka vrsta zatvarača koji može da se otvori i zatovri, iznad ovog specijalnog organa gde su bakterije. Na leđima ima detektore kako bi mogla da oseti koliko mesečine pada na njena leđa. I zatim otvara i zatvara ovaj zatvarač tako da količina svetla koja dolazi sa dna -- a koju stvaraju bakterije -- bude ista kao količina svetla koja pada sipi na leđa, kako ne bi napravila senku. Ona ustvari koristi svetlost bakterija kao sredstvo kontra-svetla, kao sistem zaštite kako predatori ne bi mogli da vide njenu senku, izračunaju njenu putanju i pojedu je. Ovo je nešto kao stelt bombarder okeana.
(Laughter)
(Smeh)
But then if you think about it, this squid has this terrible problem, because it's got this dying, thick culture of bacteria, and it can't sustain that. And so what happens is, every morning when the sun comes up, the squid goes back to sleep, it buries itself in the sand, and it's got a pump that's attached to its circadian rhythm. And when the sun comes up, it pumps out, like, 95 percent of the bacteria. So now the bacteria are dilute, that little hormone molecule is gone, so they're not making light. But, of course, the squid doesn't care, it's asleep in the sand. And as the day goes by, the bacteria double, they release the molecule, and then light comes on at night, exactly when the squid wants it.
Ali ako malo bolje razmislite, sipa ima ovaj strašan problem jer ima ovu umiruću, gustu kulturu bakterija koju ne može da održava. I šta se onda dešava, svako jutro kada se pojavi sunce sipa odlazi da spava, zakopavajući se u pesak, i ima pumpu koja je spojena sa njenim svakodnevnim ritmom, i kada sunce izađe, ona ispumpa nekih 95 procenata bakterije. Sada su bakterije razređene, onaj mali hormonski molekul je nestao, pa one ne stvaraju svetlost -- ali sipu naravno nije ni briga. Ona spava u pesku. I kako dan odmiče, bakterije se umnožavaju, ispuštaju molekul i svetlo se pojavljuje uveče, baš onda kada je sipi potrebno.
So 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 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. So 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.
Prvo smo shvatili kako to ova bakterija radi, a onda smo uzeli alate molekularne biologije da zaista shvatimo kakav je to mehanizam. I ono što smo pronašli -- ovo je ponovo moja bakterijska ćelija -- je to da Vibrio fischeri ima protein -- to je ova crvena kutijica -- to je enzim koji čini ovaj mali hormonski molekul -- crveni trougao. A zatim, kako broj ćelija raste, sve one ispuštaju taj molekul u svoju sredinu, pa tako ima mnogo molekula. A bakterija takođe ima receptor na površini ćelije koji se uklapa kao brava s ključem, sa tim molekulom. Ovi receptori su isti kao i oni na površini vaših ćelija. Kada se broj molekula poveća do određenog broja -- što govori o broju ćelija -- on se zaključava u taj receptor i informacija dolazi u ćelije i govori ćelijama da uključe to kolektivno ponašanje da prave svetlost.
Why this is interesting is because in the past decade, we have found that this is not just some anomaly of this ridiculous, glow-in-the-dark bacterium that lives in the ocean -- all bacteria have systems like this. So now what we understand is that all bacteria can talk to each other. They make chemical words, they recognize those words, and they turn on group behaviors that are only successful when all of the cells participate in unison. So now we have a fancy name for this: we call it "quorum sensing." They vote with these chemical votes, the vote gets counted, and then everybody responds to the vote.
Ovo je interesantno zbog toga što smo u prošloj deceniji otkrili da ovo nije samo neka anomalija ove smešne sija-u-mraku bakterije, koja živi u okeanu -- sve bakterije imaju ovakve sisteme. Ono što sada shvatamo jeste da sve bakterije mogu da razgovaraju međusobno. One prave hemijske reči, prepoznaju te reči, i uključuju grupno ponašanje, koje uspešno funkcioniše kada sve ćelije učestvuju zajedno. Imamo fensi ime za ovo, zovemo to kvorumska percepcija. Oni glasaju ovim hemijskim glasovima, glasovi se prebroje i onda svi odgovore na ono što je izglasano.
What's important for today's talk is we know there are hundreds of behaviors that bacteria carry out in these collective fashions. But the one that's probably the most important to you is virulence. It's not like a couple bacteria get in you and start secreting some toxins -- you're enormous; that would have no effect on you, you're huge. But what they do, we now understand, is they get in you, they wait, they start growing, they count themselves with these little molecules, and they recognize when they have the right cell number that if all of the bacteria launch their virulence attack together, they're going to be successful at overcoming an enormous host. So bacteria always control pathogenicity with quorum sensing. So that's how it works.
Ono što je važno za današnji govor, jeste to da znamo da postoji stotine ponašanja koje bakterije sprovode na ovaj zajednički način. Ali ono koje je vama verovatno najvažnije jeste zaraza. Nije to kao da nekoliko bakterija uđe u vaš organizam i počne da proizvodi neke toksine -- vi ste ogromni, to ne bi imalo nikakvog efekta na vas. Vi ste ogromni. Ono što one rade, a to sada razumemo, jeste da uđu u vaš organizam, čekaju, počnu da rastu, prebrojavaju se uz pomoć ovih malih molekula, i prepoznaju kada imaju odgovarajući broj ćelija da ako sve bakterije zajedno otpočnu svoj napad zaraze, onda uspešno mogu da savladaju ogromnog domaćina. Bakterije uvek kontrolišu oboljevanje ovom kvorumskom percepcijom. Tako to funkcioniše.
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. And 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. So 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.
Zatim smo želeli da pogledamo šta su ustvari ovi molekuli -- to su bili oni crveni trouglovi na prošlom slajdu. Ovo je molekul Vibrio fischeri. Ovo je reč uz pomoć koje govori. Onda smo počeli da posmatramo druge bakterije, i ovo je samo deo molekula koje smo otkrili. Ono što se nadam da možete da vidite jeste da su molekuli povezani. Deo molekula s leve strane je identičan kod svih vrsta bakterija. Ali desni deo molekula je pomalo drugačiji kod svake pojedinačne vrste. To je ono što ustvari daje odabranoj vrsti specifičnosti njihovih jezika. Svaki molekul uklapa se sa svojim partnerskim receptorom i ni jednim drugim. Tako da su ovo privatni, tajni razgovori. Ovi razgovori su samo za komunikaciju u okviru vrste. Svaka bakterija koristi poseban molekul, koji je njen jezik, koji omogućava prebrojavanje svojih rođaka.
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. 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.
Kada smo dotle došli, mislili smo da smo na početku shvatanja da bakterije imaju društveno ponašanje. Ali ono o čemu smo zaista razmišljali jeste da većinu vremena bakterije ne žive same, već žive u neverovatnim mešavinama sa stotinama ili hiljadama drugih vrsta bakterija. I to je prikazano na ovom slajdu. Ovo je vaša koža. Ovo je znači samo slika -- mikrograf vaše kože. Bilo gde na vašem telu, to izgleda manje više ovako, i ono što se nadam da možete da vidite, jeste da tu ima raznih vrsta bakterija. Počeli smo da razmišljamo da li je ovo zaista vezano za komunikaciju među bakterijama i o brojanju svojih suseda, i kako nije dovoljno da samo možete da razgovarate u okviru svoje vrste. Mora da postoji način da se napravi popis ostalih bakterija u okviru populacije. Zato smo se vratili molekularnoj biologiji
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." And they take that information inside, and they decide what tasks to carry out depending on who's in the minority and who's in the majority of any given population.
i počeli da proučavamo različite bakterije, i ono što smo otkrili jeste da su bakterije ustvari multilingvalne Sve one imaju sistem koji je specifičan za vrstu -- one imaju molekul koji kaže "ja". Ali pored tog, one imaju drugi, paralelan, sistem, koji smo otrkili, koji je opšti. Znači, imaju drugi enzim koji daje drugi signal i koji ima svoj sopstveni receptor, i taj molekul je bakterijski jezik razmene. Koriste ga sve različite bakterije, i to je jezik komunikacije među vrstama. Ono što se događa, jeste da bakterije mogu da prebroje koliko ima "mene" i koliko ima "tebe". One prihvataju tu informaciju, i odlučuju koji će zadatak da obave, u zavisnosti od toga ko je u manjini, a ko u većini u okviru date populacije.
Then, again, we turned to chemistry, and we figured out what this generic molecule is -- that was the pink ovals on my last slide, this is it. It's a very small, five-carbon molecule. And what the important thing is that we learned is that every bacterium has exactly the same enzyme and makes exactly the same molecule. So they're all using this molecule for interspecies communication. This is the bacterial Esperanto.
Onda smo se ponovo okrenuli hemiji, i shvatili smo šta je ovaj opšti molekul -- to su bili roze ovalni oblici na poslednjem slajdu, to je to. To je veoma mali molekul C5. Ono što je važno jeste da smo naučili, da svaka bakterija ima isti enzim i pravi potpuno isti molekul. Znači sve one koriste ovaj molekul za komunikaciju među vrstama. To je bakterijski Esperanto.
(Laughter)
(Smeh)
So once we got that far, we started to learn that bacteria can talk to each other with this chemical language. But we started to think that maybe there is something practical that we can do here as well. I've told you that bacteria have all these social behaviors, that they communicate with these molecules. Of course, I've also told you that one of the important things they do is to initiate pathogenicity using quorum sensing. So we thought: What if we made these bacteria so they can't talk or they can't hear? Couldn't these be new kinds of antibiotics?
Kada smo dotle stigli, počeli smo da učimo da bakterije razgovaraju međusobno uz pomoć ovog hemijskog jezika. Ali počeli smo da mislimo da možda postoji nešto praktično, što ovde možemo da uradimo. Rekla sam vam da bakterije imaju razna društvena ponašanja, da komuniciraju uz pomoć ovih molekula. Takođe sam vam rekla da jedna od važnih stvari koju rade jeste izazivanje bolesti uz pomoć kvorumske percepcije. Mislili smo, šta ako napravimo da bakterije ne mogu da pričaju ili ne mogu da čuju? Zar to ne bi bila nova vrsta antibiotika?
And of course, you've just heard and you already know that we're running out of antibiotics. Bacteria are incredibly multi-drug-resistant right now, and that's because all of the antibiotics that we use kill bacteria. They either pop the bacterial membrane, they make the bacterium so it can't replicate its DNA. We kill bacteria with traditional antibiotics, and that selects for resistant mutants. And so now, of course, we have this global problem in infectious diseases. So we thought, what if we could sort of do behavior modifications, just make these bacteria so they can't talk, they can't count, and they don't know to launch virulence?
Naravno, upravo ste čuli i već znate da nam ponestaje antibiotika. Bakterije su trenutno veoma otporne na razne vrste lekova, a to je zato što svi antibiotici koje koristimo ubijaju bakterije. Oni razbijaju membranu bakterije, i bakterija ne može ponovo da napravi svoj DNK. Mi ubijamo bakterije sa tradicionalnim antibioticima a to stvara otporne mutante. I zato sada imamo ovaj globalni problem kada su infektivne bolesti u pitanju. Mislili smo, šta ako bismo mogli da napravimo promene u ponašanju, da onemogućimo bakterije da razgovaraju, da ne mogu da se prebroje, i tako ne znaju da lansiraju svoj otrov.
So that's exactly what we've done, and we've sort of taken two strategies. The first one is, we've targeted the intraspecies communication system. So we made molecules that look kind of like the real molecules, which you saw, but they're a little bit different. And so they lock into those receptors, and they jam recognition of the real thing. So by targeting the red system, what we are able to do is make species-specific, or disease-specific, anti-quorum-sensing molecules. We've also done the same thing with the pink system. We've taken that universal molecule and turned it around a little bit so that we've made antagonists of the interspecies communication system. The hope is that these will be used as broad-spectrum antibiotics that work against all bacteria.
I to je upravo ono što smo uradili i napravili smo dve strategije. Prva je da smo ciljali na sistem komunikacije između vrsta. Napravili smo molekule koji izgledaju kao pravi molekuli -- koje ste videli -- ali su malo drugačiji. I tako se oni uklope sa receptorima, i blokiraju prepoznavanje prave stvari. Ciljajući crveni sistem, možemo da napravimo određenu vrstu, ili anti-kvorumske molekule za određenu bolest. Isto smo uradili i sa rozim sistemom. Uzeli smo univerzalni molekul i malo ga promenili, tako što smo napravili protivnike komunikacionom sistemu između vrsta. Nadamo se da će ovo biti upotrebljeno za različite vrste antibiotika koji rade protiv bakterija.
And so to finish, I'll show you the strategy. In this one, I'm just using the interspecies molecule, but the logic is exactly the same. So 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. And so 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 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.
Za kraj ću vam samo pokazati strategiju. U ovoj koristim samo molekule različitih vrsta ali je princip potpuno isti. Ono što znate je da kada bakterija uđe u životinju, u ovom slučaju u miša. ona ne pušta otrov odmah. Ona uđe unutra, počne da raste, počne da emituje svoje molekule za kvorumsku percepciju. Prepoznaje kada ima dovoljno bakterija da može da lansira svoj napad, i životinja umire. Ono što smo uspeli da uradimo jeste da damo ove otrovne infekcije, ali smo ih dali zajedno sa anti-kvorumskim molekulima percepcije -- to su molekuli koji izgledaju kao prava stvar, ali su malo drugačiji, što sam predstavila na ovom slajdu. Ono što sada znamo, jeste da ako lečimo životinju sa patogenom bakterijom -- patogena bakterija otporna na spektar lekova -- a u isto vreme joj dajemo naš anti-kvorumski molekul percepcije, životinja će, ipak, preživeti.
And so we think that this is the next generation of antibiotics, and it's going to get us around, at least initially, this big problem of resistance. What I hope you think is that bacteria can talk to each other, they use chemicals as their words, they have an incredibly complicated chemical lexicon that we're just now starting to learn about. Of course, what that allows bacteria to do is to be multicellular. So in the spirit of TED, they're doing things together because it makes a difference. What happens is that bacteria have these collective behaviors, and they can carry out tasks that they could never accomplish if they simply acted as individuals.
Mislimo da je ovo nova generacija antibiotika, i bar u početku ćemo uspeti da zaobiđemo ovaj veliki problem otpora. Nadam se da mislite da bakterije mogu da razgovaraju međusobno, da koriste hemikalije kao reči, da imaju neverovatno komplikovan hemijski leksikon, koji tek sada počinjemo da učimo. Naravno, to omogućava bakterijama da budu višećelijske. I u duhu TED-a one zajedno rade stvari jer to je ono što menja stvari. Ono što se dešava jeste da bakterije imaju ova kolektivna ponašanja, i mogu da izvršavaju zadatke koje nikada ne bi mogle da urade kada bi delovale pojedinačno.
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. So we think bacteria made the rules for how multicellular organization works. And we think by studying bacteria, we're going to be able to have insight about multicellularity in the human body. So 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. So by using these two molecules, they can say "me" and they can say "you." And 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.
Ono, što se nadam, da mogu dalje da vas uverim, jeste da je ovo višećelijski izum. Bakterije su na Zemlji milijardama godina. Ljudi -- nekoliko stotina hiljada. Mi mislimo da su bakterije napravile pravila za funkcionisanje višećelijske organizacije. Mi mislimo, da ćemo proučavajući bakterije, moći da steknemo uvid u to kako višećelijsko funkcioniše u ljudskom telu. Znamo da principi i pravila, ukoliko ih shvatimo kod ovih primitivnih organizama, moći će, nadamo se, da se primene i na druge bolesti čoveka, kao i na ponašanje čoveka. Nadam se da je ono što ste naučili to da bakterija može da razlikuje sebe od drugih. Koristeći ova dva molekula, one mogu da kažu "ja" i mogu da kažu "ti". Opet, naravno, to je ono što i mi radimo i na molekularnom nivou, kao i na onom spoljašnjem, vidljivom nivou, ali ja razmišljam o molekularnim stvarima.
This is exactly what happens in your body. It's not like your heart cells and kidney cells get all mixed up every day, and that's because there's all of this chemistry going on, these molecules that say who each of these groups of cells is and what their tasks should be. So again, we think bacteria invented that, and you've just evolved a few more bells and whistles, but all of the ideas are in these simple systems that we can study.
Ovo je upravo ono što se dešava u vašem telu. Nije kao da se ćelije vašeg srca i bubrega pomešaju svakog dana, a to je sve zbog ove hemije, ovih molekula koji govore koja je tačno koja grupa ćelija, i koji je njihov zadatak. Opet, mi mislimo da su bakterije to izmislile, a vi ste samo evoluirali dalje, ali sve ideje su u ovim jednostavnim sistemima koje možemo da proučavamo.
And the final thing is, just to reiterate that there's this practical part, and so we've made these anti-quorum-sensing molecules that are being developed as new kinds of therapeutics. But then, to finish with a plug for all the good and miraculous bacteria that live on the earth, we've also made pro-quorum-sensing molecules. So we've targeted those systems to make the molecules work better. So remember, you have these 10 times or more bacterial cells in you or on you, keeping you healthy. What we're also trying to do is to beef up the conversation of the bacteria that live as mutualists with you, in the hopes of making you more healthy, making those conversations better, so bacteria can do things that we want them to do better than they would be on their own.
Poslednja stvar je, da ponovim da postoji taj praktični deo, da smo napravili ove anti-kvorumske molekule percepcije koji se razvijaju kao nova vrsta lekova. Ali, da završim sa priključkom za sve dobre i čudesne bakterije koje žive na Zemlji, takođe smo napravili i pro-kvorumske molekule percepcije. Ciljali smo na one sisteme zbog kojih će molekuli raditi bolje. Setite se da imate 10 puta ili više bakterijskih ćelija u sebi ili na sebi, koje vas održavaju zdravima. Ono što takođe pokušavamo da uradimo, jeste da pojačamo razgovore bakterija koje žive u zajednici sa vama, kako bismo vas učinili zdravijim, poboljšavajući te razgovore, kako bi bakterije radile ono što mi hoćemo bolje nego što bi to one same uradile.
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. And 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 hear some talk about something ridiculous in the natural world, it was done by a child. So 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. And it's a really lucky demographic to work with.
Na kraju, htela sam da vam pokažem ovo je moje društvo na Prinstonu, Nju Džerzi. Sve što sam vam ispirčala otkrio je neko ko se nalazi na toj slici. Nadam se da kada učite stvari, kao na primer o tome kako funkcioniše svet prirode -- hoću samo da kažem da kad god pročitate nešto u novinama ili čujete nekog da priča o nečem smešnom u svetu prirode, to je uradilo dete. Nauku stvara taj deo populacije. Svi ti ljudi su između 20 i 30 godina starosti, i oni su motor koji pokreće naučna otkrića u ovoj zemlji. To je veoma srećna populacija s kojom može da se radi.
(Applause)
Ja stalno starim i starim, a oni su uvek istih godina,
I keep getting older and older, and they're always the same age. And it's just a crazy, delightful job. And I want to thank you for inviting me here, it's a big treat for me to get to come to this conference.
i to je jedan ludo izvrstan posao. Želim da vam se zahvalim što ste me pozvali ovde. Velika je poslastica za mene da budem na ovoj konferenciji. (Aplauz)
(Applause)
Thanks.
Hvala.
(Applause)
(Aplauz)