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 so najstarejši živeči organizmi na Zemlji. Ti enocelični mikroskopski organizmi obstajajo že miljarde let. Gre torej za enoceličarje, njihova značilnost pa je, da imajo enojen genski zapis. Imajo zelo malo genov, genski zapis vsebuje vse njihove značilnosti. Bakterije se preživljajo s hranili iz okolja, zrastejo in se prepolovijo, s čimer nastaneta dve novi celici in tako dalje. Stalno rastejo in se delijo -- nič posebnega -- vendar pa smo s temi bitji v izjemnem odnosu.
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.
Vem, da vi sebe vidite kot ljudi, jaz pa razmišljam tako. Ta figura predstavlja povprečnega človeka, pike na njem pa predstavljajo celice, ki sestavljajo človeško telo. Vsakega od nas sestavlja okrog bilijon človeških celic zaradi katerih lahko živimo in delujemo, poleg tega pa je v in na nas še 10 bilijonov bakterijskih celic v vsakem trenutku življenja. Na človeškem telesu je torej desetkrat več bakterijskih kot človeških celic. Šteje pa seveda le zaporedje nukleotidov A, T, G in C, ki sestavljajo vaš genski kod in pogojujejo vaše značilnosti. Imate okrog 30.000 genov. Bakterijskih genov imate stokrat več, za vas pa so pomembni celo življenje. Morda ste 10 odstotkov človek, verjetneje pa zgolj 1 odstotek, odvisno kateri vidik vam je ljubši. Vi se vidite kot ljudi, jaz pa vas vidim kot skoraj izključno bakterije.
(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.
Te bakterije niso pasivne, pač pa so izjemnega pomena, saj nas ohranjajo žive. Okrog nas ustvarjajo neviden ščit, ki nas brani pred škodljivimi vplivi okolja, da ne zbolimo. Prebavljajo nam hrano, sintetizirajo vitamine, našemu imunskemu sistemu sporočajo, naj se ubrani slabih mikrobov. Vse te neverjetne stvari počnejo, da ostanemo živi in zdravi, pa kljub temu ostajajo prezrte. Ponovno se jih pa zavemo, ko smo zaradi njih ogroženi. Na Zemlji je torej mnogo vrst bakterij, ki niso v stiku s človeškim telesom, ko pa so, lahko zaradi tega hudo zbolite.
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.
V našem laboratoriju se torej ukvarjamo s tem, ali so pomembnejši dobri ali slabi vplivi bakterij. Zanimalo nas je predvsem, kako sploh lahko kaj naredijo? Ker so izjemno majhne, jih lahko vidimo le z mikroskopom. Vse življenje le rastejo in se delijo in vedno se jih je dojemalo kot samotarske organizme. Zdelo se nam je, da so pač premajhne, da bi lahko vplivale na okolje, če delujejo individualno. Zanimalo nas je torej, ali obstaja drugačen način življenja bakterij.
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.
Namig za to nam je dala morska bakterija, imenovana Vibrio fischeri. Na sliki vidite pomočnika iz mojega laboratorija, ki drži bučko tekoče bakterijske kulture, čudovite neškodljive bakterije iz oceana, imenovane Vibrio fischeri. Njena posebnost je, da ustvarja svetlobo, torej bioluminescenco, tako kot kresnice. Tem celicam nismo dodali ničesar. Fotografijo smo posneli le z ugasnjenimi lučmi in videlo se je to.
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.
Za nas ni bilo presenetljivo to, da bakterije ustvarjajo svetlobo, pač pa kdaj jo ustvarjajo. Ugotovili smo, da v osami oz. v razredčeni suspenziji do tega ne pride. Ko pa se namnožijo do določenega števila celic, začnejo vse bakterije hkrati oddajati svetlobo. Želeli smo vedeti, kako lahko bakterije, ti preprosti organizmi, zaznajo, kdaj so same in kdaj so v skupini, da potem skupaj nekaj izvedejo. Ugotovili smo, da to dosežejo z medsebojnim sporazumevanjem, nekakšnim kemičnim jezikom. Predpostavimo, da je to naša bakterijska celica.
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.
Ko je sama, ne ustvarja svetlobe. Namesto tega proizvaja in izloča majhne molekule, ki si jih lahko predstavljate kot hormone -- predstavljajo jih rdeči trikotniki -- in ko je bakterija sama, molekule le odplavajo stran in svetlobe ni. Ko pa se bakterije pomnožijo, vse sodelujejo pri sproščanju takih molekul, izvencelična količina teh molekul se torej prav tako pomnoži v sorazmerju s številom celic. Ko molekula doseže količino, ki sporoči bakterijam, koliko sosednjih celic je, skupaj prepoznajo to molekulo in skupaj ustvarijo svetlobo. Tako deluje bioluminescenca -- sporazumevajo se s kemičnimi besedami.
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, da Vibrio fisceri to počne, je biološki. Tu je še eno morsko bitje -- ta ligenj je namreč njen gostitelj. Na sliki je ligenj Euprymna scolopes, obrnjen na hrbet in upam, da vidite dva svetleča režnja, v katerih živijo celice Vibro fischeri in v velikem številu ustvarjajo svetlobo. Ligenj te vsiljivce gosti, ker potrebuje njihovo svetlobo.
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.
Živijo v sožitju, mehkužec pa živi blizu havajskih obal v zelo nizki vodi. Ta ligenj je nočna žival, tekom dneva namreč zakopan v pesek spi, ponoči pa pride ven na lov. Zaradi plitkosti vode, kjer ligenj živi, zvezdna ali lunina svetloba zlahka prodre do morskega dna. Ligenj je razvil zaslonko, s katero odstira in zastira ta poseben organ, ki gosti bakterijo. Na hrbtu ima senzorje za določanje jakosti zvezdne ali lunine svetlobe na njem. Glede na to odpira in zapira zaslonko, da se jakost svetlobe, ki jo bakterije sproščajo na njegovi spodnji strani, natanko ujema s svetlobo na hrbtu, zato pod sabo ne ustvarja sence. S svetlobo bakterij torej osvetli osenčeno površino pod sabo, da plenilci ne zaznajo njegove sence in ga tako tudi ne morejo upleniti. Je torej nekakšen oceanski nevidni bombnik.
(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.
A pravzaprav je to zanj tudi težava, saj mu lahko ta razkrajajoča, gosta bakterijska kultura, ki jo nosi, tudi škodi. Zato se ligenj vsako jutro ob sončnem vzhodu zakoplje v pesek in preko črpalke, ki se odziva na njegov dnevni ritem, izčrpa 95 odstotkov bakterijskih celic. Bakterije so zdaj razredčene, malih hormonskih molekul ni, zato tudi ni svetlobe, kar lignja ne moti, saj spi v pesku. Preko dneva se bakterije pomnožijo, izločajo molekule in ponoči ustvarijo svetlobo, točno takrat, ko jo ligenj potrebuje.
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.
Najprej smo ugotovili, kako bakterija to izvede, nato pa smo z molekularno biologijo prišli do spoznanja o tem mehanizmu. Ugotovili smo -- to je torej ta bakterijska celica -- da Vibrio fischeri vsebuje protein -- to je rdeči kvader -- encim, ki ustvari ta rdeči trikotnik, hormonsko molekulo. Ko celice rastejo, vse oddajajo molekulo, s katero se napolne okolica. Bakterije pa imajo na celični površini tudi receptor, ki se kot ključ ujema s ključavnico -- molekulo. Taki receptorji so tudi na celičnih površinah v vašem telesu. Ko se molekula namnoži do določene vrednosti, ki sporoča število celic, se zaklene v ta receptor, podatki pa vstopijo v celice in jim sporočijo, naj izvršijo skupinsko ustvarjanje svetlobe.
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.
To je pomembno, ker smo v zadnjem desetletju dognali, da pri tej smešni morski svetleči bakteriji ne gre le za nepravilnost, pač pa imajo vse bakterije take sisteme. Zdaj je torej jasno, da imajo vse bakterije možnost sporazumevanja. Ustvarjajo kemične besede, jih prepoznavajo in se nanje skupinsko odzivajo, pri čemer morajo sodelovati vse celice, da delovanje uspe. Gre za t.i. quorum sensing (zaznavanje celične gostote oz. avtoindukcija). Glasujejo s kemičnimi glasovi, jih preštejejo in nato vse nanje odgovorijo.
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.
Pomembno je, da vemo, da bakterije na tak kolektiven način izvedejo na stotine različnih dejavnosti. Za vas najpomembejši pa je najbrž njihova sposobnost povzročiti bolezen. Ena ali dve bakterijski celici ob vstopu v telo še ne izločata toksinov -- človeško telo je namreč ogromno, preveliko, da bi nanj imeli vpliv. Zdaj torej vemo, da ob vstopu čakajo, se množijo, se preko molekul preštejejo in ko dosežejo določeno število celic, da skupaj sprožijo izbruh bolezni, bodo zmožne premagati še tako velikega gostitelja. Bakterije patogenost vedno upravljajo z avtoindukcijo. Tako to deluje.
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.
Nato smo se vrnili tudi k molekulam, rdečim trikotnikom na slikah. To je molekula bakterije Vibrio fischeri. To je beseda, s katero se sporazumeva. Začeli smo opazovati še druge bakterije in to je le delček odkritih molekul. Upam, da je vidno, kaj imajo te molekule skupnega. Levi del molekule je identičen pri prav vsaki vrsti bakterije. Desni del molekule pa je nekoliko drugačen. To v teh jezikih izraža posebne značilnosti vrste bakterije. Vsaka molekula spada zgolj k primernemu receptorju. Gre torej za zasebne, skrivne pogovore znotraj ene vrste. Vsaka bakterija z določeno molekulo ugotovi, koliko celic njene vrste jo obkroža.
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.
Verjeli smo, da začenjamo razumeti skupinsko delovanje bakterij. Seveda pa vemo, da večino časa bakterije ne živijo same, pač pa v gostih mešanicah stotin, tisočin vrst bakterij. To prikazuje ta slika. To je površina vaše kože. Gre le za sliko, približan posnetek kože. Kjerkoli na vašem telesu gre za podoben prizor in upam, da vidite, da gre za različne vrste bakterij. Pri sporazumevanju bakterij in štetju sorodnih sosed pa ni dovolj le sposobnost sporazumevanja s člani iste vrste. Obstajati mora torej tudi način popisa ostalih bakterij v okolici. Vrnili smo se k molekularni 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.
in začeli preučevati različne vrste bakterij, pri čemer smo ugotovili, da so bakterije pravzaprav večjezične. Vse imajo sistem prepoznavanja lastne vrste -- molekulo, ki pravi "jaz". A temu vzporedno smo odkrili še sistem prepoznavanja različnih članov rodu. Obstaja torej še drug encim, ki ustvari drugačen signal za drugačen receptor -- ta molekula je jezik sporazumevanja med različnimi bakterijami, uporabljajo pa ga za medvrstno sporazumevanje. Bakterije tako lahko preštejejo člane svoje in tuje vrste. Glede na podatek o večinski in manjšinski vrsti v katerikoli populaciji se odločijo, kateri postopek naj izvedejo.
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.
Nato smo se vrnili h kemiji in ugotovili sestavo te rodovne molekule -- rožnatih ovalov na zadnji sliki. To je majhna molekula s petimi atomi ogljika. Pomembno je, da ima vsaka bakterija točno enak encim in ustvari točno enako molekulo. Tako torej vse uporabljajo to molekulo za medvrstno sporazumevanje. 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?
Nato smo spoznali, da se bakterije sporazumevajo s tem kemičnim jezikom. Začelo pa nas je zanimati tudi, kako bi lahko to praktično uporabili. Delovanje bakterij je torej skupinsko, sporazumevajo pa se preko teh molekul. Pri tem je pomembno, da se patogenost začne z zaznavanjem celične gostote. Razmišljali smo, kako bi lahko vplivali na bakterije, da se ne bi mogle sporazumevati? Bi lahko ustvarili novo vrsto antibiotikov?
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?
Vsi seveda že veste, da nam zmanjkuje antibiotikov. Bakterije so dandanes odporne že na vrsto zdravil, saj antibiotiki, kot jih poznamo, bakterijo ubijejo. Učinkujejo na membrano bakterij oz. na njihovo DNK, da se ne more podvojevati. Bakterije uničujemo s tradicionalnimi antibiotiki, nastanejo pa odporni mutanti. Velik svetovni problem so seveda nalezljive bolezni. Pomislili smo, da bi lahko posegli v delovanje bakterij, da se ne bi mogle sporazumevati in preštevati, kar bi zaustavilo sprožitev bolezni.
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.
Naredili smo točno to in sicer na dva načina. Najprej je bil naš cilj sistem sporazumevanja znotraj ene vrste. Ustvarili smo molekule, ki so videti kot prave -- take, kot ste jih videli -- a so nekoliko drugačne. Ko se priklenejo na receptorje bakterij, zaustavijo prepoznavanje prave molekule. S ciljanjem na rdeči sistem lahko ustvarimo molekule prav za določeno vrsto bakterije ali bolezni, a ki ne zaznavajo celične gostote. Enako smo naredili z rožnatim sistemom. Univerzalno molekulo smo spremenili tako, da smo onemogočili tudi medvrstni sistem sporazumevanja. Upamo, da bodo taki antibiotiki široko uporabni proti vsem bakterijam.
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 konec naj predstavim to strategijo. Tu je prikazana molekula medvrstnega sporazumevanja, a način delovanja je isti. Ko bakterija pride v žival, v tem primeru v miš, bolezni ne sproži takoj. Najprej začne rasti in izločati molekule, ki zaznavajo celično gostoto. Ko bakterije dosežejo zadostno število, sprožijo bolezen in žival pogine. Vnesli smo bolezenske bakterije, a hkrati z molekulami, ki ne zaznavajo celične gostote -- molekule, ki so videti kot prave, ustrezne, a so vseeno nekoliko drugačne, kot lahko vidite. Ugotovili smo, da če žival podvržemo patogeni bakteriji, odporni na številna zdravila, in ji hkrati dodamo molekulo, ki ne zaznava celične gostote, žival preživi.
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.
Verjamemo, da je to nova generacija antibiotikov, s katerimi bomo lahko vsaj začasno premagali težavo odpornosti. Bakterije se torej lahko sporazumevajo s kemičnimi besedami, njihov izjemno zapleten nabor pa smo šele začeli spoznavati. S tem bakterije pravzaprav postanejo večcelične. Podobno kot TED tudi bakterije za dosego sprememb stavijo na sodelovanje. Obnašajo se kolektivno, s čimer izvršujejo naloge, ki jih same ne bi nikoli izvedle.
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.
Upam, da mi bo uspelo utemeljiti, da govorim o začetku večceličnosti. Bakterije so na Zemlji že milijarde let, ljudje pa le nekaj sto tisoč. Menimo, da so bakterije postavile pravila za delovanje večceličnih skupnosti. S preučevanjem bakterij želimo spoznati tudi večceličnost v človeškem telesu. Če bi nam uspelo razvozlati načela in pravila delovanja v teh preprostih organizmih, bi jih lahko uporabili tudi pri človeških boleznih in delovanju. Upam, da sem pojasnila, da bakterije znajo ločiti med sebi enakimi in drugačnimi. S tema dvema molekulama lahko rečejo "mi" in "oni". To izražamo tudi ljudje, tako na molekularni kot na beseden način, a sedaj je govora o molekularnem.
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.
Točno to se torej dogaja v vašem telesu. Celice vašega srca in ledvic se ne mešajo med sabo, saj jim na kemični način molekule povejo, kdo spada h kateri skupini celic in kaj je njihova naloga. Menimo, da so tak način iznašle bakterije. Človeško telo je sicer razvilo nekoliko bolj zapletene celice, a enak princip se vrši v teh preprostih sistemih, ki jih preučujemo.
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.
V praktičnem delu smo torej razvili molekule, ki ne zaznavajo celične gostote, da bi ustvarili nova zdravila. Da pa ne bi pozabili na vse koristne in čudovite bakterije na Zemlji, smo razvili tudi molekule, ki zaznavajo celično gostoto. Na te sisteme smo se osredotočili, da bi tako izboljšali delovanje molekul. Ne pozabite, da je na in v vašem telesu desetkrat več bakterijskih celic, ki vas ohranjajo zdrave. Poleg tega smo želeli izboljšati pogovore med bakterijami, ki živijo z vami v sožitju, da bi na vaše zdravje in delovanje učinkovale bolje, kot bi sicer same zase.
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.
Za konec vam želim še pokazati mojo družbo na Princetonu v New Jerseyu. Vse, o čemer sem vam pripovedovala, je odkrila oseba na tej sliki. Upam, da se zavedate, da dejstva, ki se jih učite, jih preberete v časopisu ali o njih slišite na predavanju o neverjetnih naravoslovnih odkritjih, so odkrili mladi ljudje. Znanost se odvija v tej starostni skupini. Vsi od njih so stari med dvajset in trideset let in predstavljajo gonilo znanstvenih odkritij v tej državi. Krasno je sodelovati z njimi.
(Applause)
Jaz se staram, ta skupina pa je vedno enakih let,
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.
zato v tem delu res izjemno uživam. Najlepša hvala za vabilo. Zelo sem vesela sem, da sem lahko sodelovala na tej konferenci. (Aplavz)
(Applause)
Thanks.
Hvala.
(Applause)
(Aplavz)