Bonnie Bassler: The secret, social lives of bacteria

296,679 views ・ 2009-04-08

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Translator: Lenka Tušar Reviewer: Tilen Pigac - EFZG
Bakterije so najstarejši živeči organizmi na Zemlji.
00:19
Bacteria are the oldest living organisms on the earth.
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00:21
They've been here for billions of years,
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Ti enocelični mikroskopski organizmi
00:23
and what they are are single-celled microscopic organisms.
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obstajajo že miljarde let.
00:27
So they're one cell
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Gre torej za enoceličarje, njihova značilnost pa je,
00:29
and they have this special property that they only have one piece of DNA.
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da imajo enojen genski zapis.
00:32
So they have very few genes and genetic information
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Imajo zelo malo genov,
genski zapis vsebuje vse njihove značilnosti.
00:35
to encode all of the traits that they carry out.
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00:38
And the way bacteria make a living is that they consume nutrients
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Bakterije se preživljajo
s hranili iz okolja,
00:42
from the environment,
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00:43
they grow to twice their size,
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zrastejo in se prepolovijo,
00:45
they cut themselves down in the middle,
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s čimer nastaneta dve novi celici in tako dalje.
00:47
and one cell becomes two, and so on and so on.
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00:49
They just grow and divide and grow and divide -- so a kind of boring life,
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Stalno rastejo in se delijo -- nič posebnega --
00:53
except that what I would argue is that you have an amazing interaction
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vendar pa smo s temi bitji
v izjemnem odnosu.
00:57
with these critters.
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00:58
I know you guys think of yourself as humans,
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Vem, da vi sebe vidite kot ljudi, jaz pa razmišljam tako.
01:00
and this is sort of how I think of you.
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Ta figura predstavlja
01:02
This man is supposed to represent a generic human being,
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povprečnega človeka,
01:05
and all of the circles in that man are all the cells that make up your body.
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pike na njem pa predstavljajo celice, ki sestavljajo človeško telo.
01:09
There's about a trillion human cells that make each one of us who we are
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Vsakega od nas sestavlja okrog bilijon človeških celic
zaradi katerih lahko živimo in delujemo,
01:13
and able to do all the things that we do.
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poleg tega pa je v in na nas še 10 bilijonov bakterijskih celic
01:16
But you have 10 trillion bacterial cells in you or on you
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v vsakem trenutku življenja.
01:19
at any moment in your life.
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01:20
So, 10 times more bacterial cells than human cells on a human being.
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Na človeškem telesu je torej
desetkrat več bakterijskih kot človeških celic.
01:25
And, of course, it's the DNA that counts,
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Šteje pa seveda le zaporedje nukleotidov
01:27
so here's all the A, T, Gs and Cs that make up your genetic code
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A, T, G in C,
ki sestavljajo vaš genski kod in pogojujejo vaše značilnosti.
01:30
and give you all your charming characteristics.
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Imate okrog 30.000 genov.
01:33
You have about 30,000 genes.
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01:34
Well, it turns out you have 100 times more bacterial genes
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Bakterijskih genov imate stokrat več,
za vas pa so pomembni celo življenje.
01:38
playing a role in you or on you all of your life.
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01:41
So at the best, you're 10 percent human; more likely, about one percent human,
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Morda ste 10 odstotkov človek,
verjetneje pa zgolj 1 odstotek,
01:46
depending on which of these metrics you like.
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odvisno kateri vidik vam je ljubši.
01:48
I know you think of yourself as human beings,
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Vi se vidite kot ljudi,
jaz pa vas vidim kot skoraj izključno bakterije.
01:51
but I think of you as 90 or 99 percent bacterial.
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01:54
(Laughter)
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(Smeh)
01:55
And these bacteria are not passive riders.
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Te bakterije niso pasivne,
01:58
These are incredibly important; they keep us alive.
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pač pa so izjemnega pomena, saj nas ohranjajo žive.
02:01
They cover us in an invisible body armor
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Okrog nas ustvarjajo neviden ščit,
02:04
that keeps environmental insults out so that we stay healthy.
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ki nas brani pred škodljivimi vplivi okolja,
da ne zbolimo.
02:08
They digest our food, they make our vitamins,
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Prebavljajo nam hrano, sintetizirajo vitamine,
02:10
they actually educate your immune system to keep bad microbes out.
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našemu imunskemu sistemu sporočajo,
naj se ubrani slabih mikrobov.
Vse te neverjetne stvari počnejo,
02:15
So they do all these amazing things
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da ostanemo živi in zdravi,
02:17
that help us and are vital for keeping us alive,
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02:20
and they never get any press for that.
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pa kljub temu ostajajo prezrte.
02:22
But they get a lot of press because they do a lot of terrible things as well.
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Ponovno se jih pa zavemo,
ko smo zaradi njih ogroženi.
Na Zemlji je torej mnogo vrst bakterij,
02:27
So there's all kinds of bacteria on the earth
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02:29
that have no business being in you or on you at any time,
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ki niso v stiku s človeškim telesom,
ko pa so, lahko zaradi tega hudo zbolite.
02:33
and if they are, they make you incredibly sick.
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02:36
And so the question for my lab
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V našem laboratoriju se torej ukvarjamo s tem,
02:38
is whether you want to think about all the good things that bacteria do
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ali so pomembnejši dobri ali slabi vplivi bakterij.
02:41
or all the bad things that bacteria do.
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02:43
The question we had is: How could they do anything at all?
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Zanimalo nas je predvsem, kako sploh lahko kaj naredijo?
Ker so izjemno majhne,
02:46
I mean, they're incredibly small.
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02:47
You have to have a microscope to see one.
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jih lahko vidimo le z mikroskopom.
02:49
They live this sort of boring life where they grow and divide,
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Vse življenje le rastejo in se delijo
02:52
and they've always been considered to be these asocial, reclusive organisms.
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in vedno se jih je dojemalo kot samotarske organizme.
02:57
And so it seemed to us that they're just too small
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Zdelo se nam je, da so pač premajhne,
03:00
to have an impact on the environment
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da bi lahko vplivale na okolje,
03:02
if they simply act as individuals.
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če delujejo individualno.
03:04
So we wanted to think if there couldn't be a different way that bacteria live.
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Zanimalo nas je torej, ali obstaja
drugačen način življenja bakterij.
Namig za to nam je dala morska bakterija,
03:09
And the clue to this came from another marine bacterium,
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03:12
and it's a bacterium called "Vibrio fischeri."
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imenovana Vibrio fischeri.
03:15
What you're looking at on this slide is just a person from my lab
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Na sliki vidite pomočnika iz mojega laboratorija,
03:18
holding a flask of a liquid culture of a bacterium,
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ki drži bučko tekoče bakterijske kulture,
čudovite neškodljive bakterije iz oceana,
03:22
a harmless, beautiful bacterium that comes from the ocean,
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imenovane Vibrio fischeri.
03:25
named Vibrio fischeri.
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03:26
And this bacterium has the special property that it makes light,
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Njena posebnost je, da ustvarja svetlobo,
torej bioluminescenco,
03:30
so it makes bioluminescence,
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03:31
like fireflies make light.
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tako kot kresnice.
03:33
We're not doing anything to the cells here,
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Tem celicam nismo dodali ničesar.
03:35
we just took the picture by turning the lights off in the room,
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Fotografijo smo posneli le z ugasnjenimi lučmi
in videlo se je to.
03:38
and this is what we see.
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03:39
And what's actually interesting to us was not that the bacteria made light
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Za nas ni bilo presenetljivo to,
da bakterije ustvarjajo svetlobo,
03:43
but when the bacteria made light.
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pač pa kdaj jo ustvarjajo.
03:45
What we noticed is when the bacteria were alone,
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Ugotovili smo, da v osami
03:48
so when they were in dilute suspension,
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oz. v razredčeni suspenziji do tega ne pride.
03:50
they made no light.
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Ko pa se namnožijo do določenega števila celic,
03:52
But when they grew to a certain cell number,
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začnejo vse bakterije hkrati oddajati svetlobo.
03:54
all the bacteria turned on light simultaneously.
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03:57
So the question that we had is:
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Želeli smo vedeti, kako lahko bakterije, ti preprosti organizmi,
03:59
How can bacteria, these primitive organisms,
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zaznajo, kdaj so same
04:02
tell the difference from times when they're alone
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in kdaj so v skupini,
04:04
and times when they're in a community,
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da potem skupaj nekaj izvedejo.
04:06
and then all do something together?
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Ugotovili smo, da to dosežejo z medsebojnim sporazumevanjem,
04:09
And what we figured out is that the way they do that is they talk to each other,
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nekakšnim kemičnim jezikom.
04:13
and they talk with a chemical language.
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Predpostavimo, da je to naša bakterijska celica.
04:15
So this is now supposed to be my bacterial cell.
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Ko je sama, ne ustvarja svetlobe.
04:18
When it's alone, it doesn't make any light.
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04:20
But what it does do is to make and secrete small molecules
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Namesto tega proizvaja in izloča majhne molekule,
04:24
that you can think of like hormones,
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ki si jih lahko predstavljate kot hormone --
04:26
and these are the red triangles.
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predstavljajo jih rdeči trikotniki -- in ko je bakterija sama,
04:28
And when the bacteria are alone, the molecules just float away,
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molekule le odplavajo stran in svetlobe ni.
04:31
and so, no light.
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04:32
But when the bacteria grow and double
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Ko pa se bakterije pomnožijo,
04:34
and they're all participating in making these molecules,
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vse sodelujejo pri sproščanju takih molekul,
izvencelična količina teh molekul se torej prav tako pomnoži
04:38
the molecule, the extracellular amount of that molecule,
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04:41
increases in proportion to cell number.
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v sorazmerju s številom celic.
04:44
And when the molecule hits a certain amount
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Ko molekula doseže količino,
04:46
that tells the bacteria how many neighbors there are,
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ki sporoči bakterijam, koliko sosednjih celic je,
04:49
they recognize that molecule
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skupaj prepoznajo to molekulo
04:51
and all of the bacteria turn on light in synchrony.
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in skupaj ustvarijo svetlobo.
04:54
And so that's how bioluminescence works --
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Tako deluje bioluminescenca --
04:56
they're talking with these chemical words.
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sporazumevajo se s kemičnimi besedami.
Razlog, da Vibrio fisceri to počne, je biološki.
04:59
The reason Vibrio fischeri is doing that comes from the biology --
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05:02
again, another plug for the animals in the ocean.
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Tu je še eno morsko bitje --
ta ligenj je namreč njen gostitelj.
05:06
Vibrio fischeri lives in this squid.
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05:08
What you're looking at is the Hawaiian bobtail squid.
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Na sliki je ligenj Euprymna scolopes,
obrnjen na hrbet
05:11
It's been turned on its back,
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05:12
and what I hope you can see are these two glowing lobes.
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in upam, da vidite dva svetleča režnja,
05:15
These house the Vibrio fischeri cells.
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v katerih živijo celice Vibro fischeri
05:18
They live in there, at high cell number.
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in v velikem številu
05:20
That molecule is there, and they're making light.
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ustvarjajo svetlobo.
Ligenj te vsiljivce gosti,
05:23
And the reason the squid is willing to put up with these shenanigans
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ker potrebuje njihovo svetlobo.
05:26
is because it wants that light.
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Živijo v sožitju,
05:28
The way that this symbiosis works
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mehkužec pa živi blizu havajskih obal
05:30
is that this little squid lives just off the coast of Hawaii,
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05:33
just in sort of shallow knee-deep water.
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v zelo nizki vodi.
05:35
And the squid is nocturnal,
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Ta ligenj je nočna žival, tekom dneva
05:37
so during the day, it buries itself in the sand and sleeps.
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namreč zakopan v pesek spi,
ponoči pa pride ven na lov.
05:41
But then at night, it has to come out to hunt.
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05:43
So on bright nights
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Zaradi plitkosti vode, kjer ligenj živi,
05:44
when there's lots of starlight or moonlight,
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zvezdna ali lunina svetloba
05:46
that light can penetrate the depth of the water the squid lives in,
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zlahka prodre do morskega dna.
05:50
since it's just in those couple feet of water.
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Ligenj je razvil zaslonko,
05:52
What the squid has developed is a shutter that can open and close
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s katero odstira in zastira ta poseben organ, ki gosti bakterijo.
05:55
over the specialized light organ housing the bacteria.
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Na hrbtu ima senzorje za določanje
05:59
And then it has detectors on its back
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jakosti zvezdne ali lunine svetlobe na njem.
06:01
so it can sense how much starlight or moonlight is hitting its back.
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06:04
And it opens and closes the shutter
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Glede na to odpira in zapira zaslonko,
06:06
so the amount of light coming out of the bottom,
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da se jakost svetlobe, ki jo bakterije
06:08
which is made by the bacterium,
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sproščajo na njegovi spodnji strani,
06:10
exactly matches how much light hits the squid's back,
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natanko ujema s svetlobo na hrbtu,
06:12
so the squid doesn't make a shadow.
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zato pod sabo ne ustvarja sence.
06:14
So it actually uses the light from the bacteria
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S svetlobo bakterij torej
06:17
to counter-illuminate itself in an antipredation device,
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osvetli osenčeno površino pod sabo,
da plenilci ne zaznajo njegove sence
06:21
so predators can't see its shadow,
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in ga tako tudi ne morejo upleniti.
06:23
calculate its trajectory and eat it.
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Je torej nekakšen oceanski nevidni bombnik.
06:25
So this is like the stealth bomber of the ocean.
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06:27
(Laughter)
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(Smeh)
06:28
But then if you think about it, this squid has this terrible problem,
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A pravzaprav je to zanj tudi težava,
saj mu lahko ta razkrajajoča, gosta bakterijska kultura,
06:32
because it's got this dying, thick culture of bacteria,
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06:34
and it can't sustain that.
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ki jo nosi, tudi škodi.
06:36
And so what happens is, every morning when the sun comes up,
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Zato se ligenj vsako jutro ob sončnem vzhodu
zakoplje v pesek in preko črpalke,
06:39
the squid goes back to sleep, it buries itself in the sand,
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ki se odziva na njegov dnevni ritem,
06:42
and it's got a pump that's attached to its circadian rhythm.
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izčrpa 95 odstotkov bakterijskih celic.
06:45
And when the sun comes up, it pumps out, like, 95 percent of the bacteria.
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06:49
So now the bacteria are dilute,
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Bakterije so zdaj razredčene, malih hormonskih molekul ni,
06:51
that little hormone molecule is gone, so they're not making light.
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zato tudi ni svetlobe,
06:54
But, of course, the squid doesn't care, it's asleep in the sand.
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kar lignja ne moti, saj spi v pesku.
Preko dneva se bakterije pomnožijo,
06:57
And as the day goes by, the bacteria double,
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izločajo molekule in ponoči ustvarijo svetlobo,
06:59
they release the molecule, and then light comes on at night,
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točno takrat, ko jo ligenj potrebuje.
07:02
exactly when the squid wants it.
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07:04
So first, we figured out how this bacterium does this,
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Najprej smo ugotovili, kako bakterija to izvede,
07:07
but then we brought the tools of molecular biology to this
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nato pa smo z molekularno biologijo
07:10
to figure out, really, what's the mechanism.
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prišli do spoznanja o tem mehanizmu.
07:12
And what we found -- so this is now supposed to be my bacterial cell --
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Ugotovili smo -- to je torej ta bakterijska celica --
07:16
is that Vibrio fischeri has a protein.
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da Vibrio fischeri vsebuje protein --
07:18
That's the red box --
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to je rdeči kvader -- encim, ki ustvari
07:20
it's an enzyme that makes that little hormone molecule,
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ta rdeči trikotnik, hormonsko molekulo.
07:23
the red triangle.
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07:24
And then as the cells grow,
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Ko celice rastejo, vse oddajajo molekulo,
07:25
they're all releasing that molecule into the environment,
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s katero se napolne okolica.
07:28
so there's lots of molecule there.
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Bakterije pa imajo na celični površini tudi receptor,
07:30
And the bacteria also have a receptor on their cell surface
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07:33
that fits like a lock and key with that molecule.
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ki se kot ključ ujema s ključavnico -- molekulo.
07:36
These are just like the receptors on the surfaces of your cells.
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Taki receptorji so tudi na celičnih površinah v vašem telesu.
Ko se molekula namnoži do določene vrednosti,
07:40
So when the molecule increases to a certain amount,
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07:42
which says something about the number of cells,
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ki sporoča število celic,
07:44
it locks down into that receptor
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se zaklene v ta receptor,
07:46
and information comes into the cells
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podatki pa vstopijo v celice
in jim sporočijo, naj izvršijo
07:49
that tells the cells to turn on this collective behavior of making light.
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skupinsko ustvarjanje svetlobe.
07:53
Why this is interesting is because in the past decade,
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To je pomembno, ker smo v zadnjem desetletju dognali,
07:56
we have found that this is not just some anomaly
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da pri tej smešni morski svetleči bakteriji
07:58
of this ridiculous, glow-in-the-dark bacterium that lives in the ocean --
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ne gre le za nepravilnost,
pač pa imajo vse bakterije take sisteme.
08:02
all bacteria have systems like this.
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08:04
So now what we understand is that all bacteria can talk to each other.
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Zdaj je torej jasno, da imajo vse bakterije možnost sporazumevanja.
08:07
They make chemical words, they recognize those words,
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Ustvarjajo kemične besede, jih prepoznavajo
08:10
and they turn on group behaviors
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in se nanje skupinsko odzivajo,
08:12
that are only successful when all of the cells participate in unison.
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pri čemer morajo sodelovati vse celice, da delovanje uspe.
08:17
So now we have a fancy name for this: we call it "quorum sensing."
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Gre za t.i. quorum sensing (zaznavanje celične gostote oz. avtoindukcija).
08:20
They vote with these chemical votes,
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Glasujejo s kemičnimi glasovi,
08:22
the vote gets counted, and then everybody responds to the vote.
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jih preštejejo in nato vse nanje odgovorijo.
08:26
What's important for today's talk is we know there are hundreds of behaviors
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Pomembno je, da vemo,
da bakterije na tak kolektiven način
08:30
that bacteria carry out in these collective fashions.
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izvedejo na stotine različnih dejavnosti.
08:33
But the one that's probably the most important to you is virulence.
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Za vas najpomembejši pa je najbrž njihova sposobnost povzročiti bolezen.
Ena ali dve bakterijski celici ob vstopu v telo
08:37
It's not like a couple bacteria get in you and start secreting some toxins --
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še ne izločata toksinov --
08:41
you're enormous; that would have no effect on you, you're huge.
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človeško telo je namreč ogromno, preveliko, da bi nanj imeli vpliv.
Zdaj torej vemo,
08:45
But what they do, we now understand,
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08:47
is they get in you, they wait, they start growing,
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da ob vstopu čakajo, se množijo,
08:50
they count themselves with these little molecules,
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se preko molekul preštejejo
08:52
and they recognize when they have the right cell number
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2635
in ko dosežejo določeno število celic,
da skupaj sprožijo izbruh bolezni,
08:55
that if all of the bacteria launch their virulence attack together,
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08:58
they're going to be successful at overcoming an enormous host.
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bodo zmožne premagati še tako velikega gostitelja.
09:02
So bacteria always control pathogenicity with quorum sensing.
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Bakterije patogenost vedno upravljajo z avtoindukcijo.
Tako to deluje.
09:07
So that's how it works.
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Nato smo se vrnili tudi k molekulam,
09:09
We also then went to look at what are these molecules.
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09:11
These were the red triangles on my slides before.
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rdečim trikotnikom na slikah.
09:14
This is the Vibrio fischeri molecule.
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2292
To je molekula bakterije Vibrio fischeri.
09:16
This is the word that it talks with.
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To je beseda, s katero se sporazumeva.
09:18
And then we started to look at other bacteria,
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Začeli smo opazovati še druge bakterije
09:20
and these are just a smattering of the molecules that we've discovered.
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in to je le delček odkritih molekul.
Upam, da je vidno,
09:24
What I hope you can see is that the molecules are related.
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kaj imajo te molekule skupnega.
09:27
The left-hand part of the molecule is identical
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2444
Levi del molekule je identičen
09:29
in every single species of bacteria.
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569793
2603
pri prav vsaki vrsti bakterije.
09:32
But the right-hand part of the molecule is a little bit different
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3086
Desni del molekule pa je nekoliko drugačen.
09:35
in every single species.
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1486
To v teh jezikih izraža
09:37
What that does is to confer exquisite species specificities to these languages.
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posebne značilnosti vrste bakterije.
09:42
So each molecule fits into its partner receptor
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3242
Vsaka molekula spada zgolj k primernemu receptorju.
09:45
and no other.
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585829
1157
Gre torej za zasebne, skrivne pogovore
09:47
So these are private, secret conversations.
209
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2858
09:49
These conversations are for intraspecies communication.
210
589892
3815
znotraj ene vrste.
09:53
Each bacteria uses a particular molecule that's its language
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593731
4192
Vsaka bakterija z določeno molekulo ugotovi,
09:57
that allows it to count its own siblings.
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3210
koliko celic njene vrste jo obkroža.
Verjeli smo, da začenjamo razumeti
10:02
Once we got that far,
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1220
10:03
we thought we were starting to understand that bacteria have these social behaviors.
214
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3972
skupinsko delovanje bakterij.
Seveda pa vemo, da večino časa
10:07
But what we were really thinking about is that most of the time,
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3055
bakterije ne živijo same, pač pa v gostih mešanicah
10:10
bacteria don't live by themselves, they live in incredible mixtures,
216
610508
3251
stotin, tisočin vrst bakterij.
10:13
with hundreds or thousands of other species of bacteria.
217
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2805
10:16
And that's depicted on this slide.
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1709
To prikazuje ta slika. To je površina vaše kože.
10:18
This is your skin.
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1156
10:19
So this is just a picture -- a micrograph of your skin.
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3018
Gre le za sliko, približan posnetek kože.
10:22
Anywhere on your body, it looks pretty much like this.
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622567
2564
Kjerkoli na vašem telesu gre za podoben prizor
in upam, da vidite, da gre za različne vrste bakterij.
10:25
What I hope you can see
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625155
1242
10:26
is that there's all kinds of bacteria there.
223
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2115
10:28
And so we started to think, if this really is about communication in bacteria,
224
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4127
Pri sporazumevanju bakterij in štetju sorodnih sosed
10:32
and it's about counting your neighbors,
225
632711
1920
pa ni dovolj le sposobnost
10:34
it's not enough to be able to only talk within your species.
226
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3618
sporazumevanja s člani iste vrste.
Obstajati mora torej tudi način
10:38
There has to be a way to take a census
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638297
2204
popisa ostalih bakterij v okolici.
10:40
of the rest of the bacteria in the population.
228
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2456
Vrnili smo se k molekularni biologiji
10:43
So we went back to molecular biology
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2051
in začeli preučevati različne vrste bakterij,
10:45
and started studying different bacteria.
230
645080
1949
pri čemer smo ugotovili,
10:47
And what we've found now is that, in fact, bacteria are multilingual.
231
647053
4003
da so bakterije pravzaprav večjezične.
Vse imajo sistem prepoznavanja lastne vrste --
10:51
They all have a species-specific system,
232
651080
2976
molekulo, ki pravi "jaz".
10:54
they have a molecule that says "me."
233
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1822
10:55
But then running in parallel to that is a second system
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2770
A temu vzporedno smo odkrili še
10:58
that we've discovered, that's generic.
235
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2071
sistem prepoznavanja različnih članov rodu.
11:00
So they have a second enzyme that makes a second signal,
236
660815
3061
Obstaja torej še drug encim, ki ustvari drugačen signal
11:03
and it has its own receptor,
237
663900
1679
za drugačen receptor --
11:05
and this molecule is the trade language of bacteria.
238
665603
3453
ta molekula je jezik sporazumevanja med različnimi bakterijami,
uporabljajo pa ga
11:09
It's used by all different bacteria,
239
669080
1976
za medvrstno sporazumevanje.
11:11
and it's the language of interspecies communication.
240
671080
3443
11:14
What happens is that bacteria are able to count
241
674547
3509
Bakterije tako lahko preštejejo člane
svoje in tuje vrste.
11:18
how many of "me" and how many of "you."
242
678080
2098
11:20
And they take that information inside,
243
680202
2068
Glede na podatek
11:22
and they decide what tasks to carry out
244
682294
2762
o večinski in manjšinski vrsti
v katerikoli populaciji se odločijo,
11:25
depending on who's in the minority and who's in the majority
245
685080
3019
11:28
of any given population.
246
688123
1944
kateri postopek naj izvedejo.
11:30
Then, again, we turned to chemistry,
247
690853
2105
Nato smo se vrnili h kemiji
11:32
and we figured out what this generic molecule is --
248
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2479
in ugotovili sestavo te rodovne molekule --
11:35
that was the pink ovals on my last slide, this is it.
249
695485
3152
rožnatih ovalov na zadnji sliki.
11:38
It's a very small, five-carbon molecule.
250
698661
2728
To je majhna molekula s petimi atomi ogljika.
Pomembno je,
11:41
And what the important thing is that we learned
251
701413
2260
11:43
is that every bacterium has exactly the same enzyme
252
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2809
da ima vsaka bakterija točno enak encim
11:46
and makes exactly the same molecule.
253
706530
2187
in ustvari točno enako molekulo.
11:48
So they're all using this molecule for interspecies communication.
254
708741
3790
Tako torej vse uporabljajo to molekulo
za medvrstno sporazumevanje.
11:52
This is the bacterial Esperanto.
255
712555
2680
To je bakterijski esperanto.
11:55
(Laughter)
256
715259
1423
(Smeh)
11:56
So once we got that far,
257
716706
1384
Nato smo spoznali,
11:58
we started to learn that bacteria can talk to each other
258
718114
2634
da se bakterije sporazumevajo s tem kemičnim jezikom.
12:00
with this chemical language.
259
720772
1350
Začelo pa nas je zanimati tudi,
12:02
But we started to think
260
722146
1150
12:03
that maybe there is something practical that we can do here as well.
261
723320
3354
kako bi lahko to praktično uporabili.
Delovanje bakterij je torej skupinsko,
12:06
I've told you that bacteria have all these social behaviors,
262
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2857
sporazumevajo pa se preko teh molekul.
12:09
that they communicate with these molecules.
263
729579
2062
12:11
Of course, I've also told you that one of the important things they do
264
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3331
Pri tem je pomembno,
da se patogenost začne z zaznavanjem celične gostote.
12:15
is to initiate pathogenicity using quorum sensing.
265
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3036
Razmišljali smo, kako bi lahko vplivali na bakterije,
12:18
So we thought:
266
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1153
12:19
What if we made these bacteria so they can't talk or they can't hear?
267
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3728
da se ne bi mogle sporazumevati?
Bi lahko ustvarili novo vrsto antibiotikov?
12:23
Couldn't these be new kinds of antibiotics?
268
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2649
12:25
And of course, you've just heard and you already know
269
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2477
Vsi seveda že veste,
da nam zmanjkuje antibiotikov.
12:28
that we're running out of antibiotics.
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1849
Bakterije so dandanes odporne že na vrsto zdravil,
12:30
Bacteria are incredibly multi-drug-resistant right now,
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2708
12:32
and that's because all of the antibiotics that we use kill bacteria.
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3977
saj antibiotiki, kot jih poznamo, bakterijo ubijejo.
12:36
They either pop the bacterial membrane,
273
756789
2110
Učinkujejo na membrano bakterij
12:38
they make the bacterium so it can't replicate its DNA.
274
758923
2903
oz. na njihovo DNK, da se ne more podvojevati.
12:41
We kill bacteria with traditional antibiotics,
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2394
Bakterije uničujemo s tradicionalnimi antibiotiki,
12:44
and that selects for resistant mutants.
276
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2526
nastanejo pa odporni mutanti.
12:46
And so now, of course, we have this global problem
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2749
Velik svetovni problem so seveda
12:49
in infectious diseases.
278
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1658
nalezljive bolezni.
12:51
So we thought, what if we could sort of do behavior modifications,
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3372
Pomislili smo, da bi lahko posegli v delovanje bakterij,
12:54
just make these bacteria so they can't talk, they can't count,
280
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3388
da se ne bi mogle sporazumevati in preštevati,
kar bi zaustavilo sprožitev bolezni.
12:58
and they don't know to launch virulence?
281
778081
2401
13:00
So that's exactly what we've done,
282
780506
1681
Naredili smo točno to in sicer na dva načina.
13:02
and we've sort of taken two strategies.
283
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1908
Najprej je bil naš cilj
13:04
The first one is, we've targeted the intraspecies communication system.
284
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4189
sistem sporazumevanja znotraj ene vrste.
13:08
So we made molecules that look kind of like the real molecules, which you saw,
285
788356
4225
Ustvarili smo molekule, ki so videti kot prave --
take, kot ste jih videli -- a so nekoliko drugačne.
13:12
but they're a little bit different.
286
792605
1710
Ko se priklenejo na receptorje bakterij,
13:14
And so they lock into those receptors,
287
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1855
zaustavijo prepoznavanje prave molekule.
13:16
and they jam recognition of the real thing.
288
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2746
13:18
So by targeting the red system,
289
798988
1929
S ciljanjem na rdeči sistem lahko ustvarimo
13:20
what we are able to do is make species-specific, or disease-specific,
290
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4946
molekule prav za določeno vrsto bakterije ali bolezni,
a ki ne zaznavajo celične gostote.
13:25
anti-quorum-sensing molecules.
291
805911
1835
13:27
We've also done the same thing with the pink system.
292
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2589
Enako smo naredili z rožnatim sistemom.
13:30
We've taken that universal molecule and turned it around a little bit
293
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3430
Univerzalno molekulo smo spremenili tako,
13:33
so that we've made antagonists of the interspecies communication system.
294
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4219
da smo onemogočili tudi
medvrstni sistem sporazumevanja.
Upamo, da bodo taki antibiotiki široko uporabni
13:38
The hope is that these will be used as broad-spectrum antibiotics
295
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4227
13:42
that work against all bacteria.
296
822331
1966
proti vsem bakterijam.
13:44
And so to finish, I'll show you the strategy.
297
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2760
Za konec naj predstavim to strategijo.
13:47
In this one, I'm just using the interspecies molecule,
298
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2662
Tu je prikazana molekula medvrstnega sporazumevanja,
13:49
but the logic is exactly the same.
299
829791
2119
a način delovanja je isti.
13:51
So what you know is that when that bacterium gets into the animal --
300
831934
3253
Ko bakterija pride v žival,
v tem primeru v miš,
13:55
in this case, a mouse --
301
835211
1169
13:56
it doesn't initiate virulence right away.
302
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2395
bolezni ne sproži takoj.
13:58
It gets in, it starts growing,
303
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1715
Najprej začne rasti in izločati molekule,
14:00
it starts secreting its quorum-sensing molecules.
304
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2846
ki zaznavajo celično gostoto.
14:03
It recognizes when it has enough bacteria
305
843432
2374
Ko bakterije dosežejo zadostno število,
14:05
that now they're going to launch their attack,
306
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2164
sprožijo bolezen
in žival pogine.
14:08
and the animal dies.
307
848018
1303
14:09
And so what we've been able to do is to give these virulent infections,
308
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3543
Vnesli smo bolezenske bakterije,
14:12
but we give them in conjunction with our anti-quorum-sensing molecules.
309
852912
3843
a hkrati z molekulami, ki ne zaznavajo celične gostote --
14:16
So these are molecules that look kind of like the real thing,
310
856779
2858
molekule, ki so videti kot prave, ustrezne,
a so vseeno nekoliko drugačne, kot lahko vidite.
14:19
but they're a little different, which I've depicted on this slide.
311
859661
3113
Ugotovili smo, da če žival podvržemo
14:22
What we now know is that if we treat the animal with a pathogenic bacterium --
312
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3725
patogeni bakteriji, odporni na številna zdravila,
14:26
a multi-drug-resistant pathogenic bacterium --
313
866547
2277
14:28
in the same time we give our anti-quorum-sensing molecule,
314
868848
4024
in ji hkrati dodamo molekulo, ki ne zaznava celične gostote,
14:32
in fact, the animal lives.
315
872896
1879
žival preživi.
14:34
And so we think that this is the next generation of antibiotics,
316
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3228
Verjamemo, da je to nova generacija antibiotikov,
14:38
and it's going to get us around, at least initially,
317
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2489
s katerimi bomo lahko vsaj začasno
14:40
this big problem of resistance.
318
880564
2174
premagali težavo odpornosti.
14:42
What I hope you think is that bacteria can talk to each other,
319
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3233
Bakterije se torej lahko sporazumevajo
s kemičnimi besedami,
14:46
they use chemicals as their words,
320
886019
2150
14:48
they have an incredibly complicated chemical lexicon
321
888193
3086
njihov izjemno zapleten nabor
14:51
that we're just now starting to learn about.
322
891303
2733
pa smo šele začeli spoznavati.
S tem bakterije pravzaprav
14:54
Of course, what that allows bacteria to do is to be multicellular.
323
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4828
postanejo večcelične.
14:58
So in the spirit of TED,
324
898912
1805
Podobno kot TED tudi bakterije
15:00
they're doing things together because it makes a difference.
325
900741
3876
za dosego sprememb stavijo na sodelovanje.
Obnašajo se kolektivno,
15:04
What happens is that bacteria have these collective behaviors,
326
904641
3282
15:07
and they can carry out tasks
327
907947
1789
s čimer izvršujejo naloge,
15:09
that they could never accomplish if they simply acted as individuals.
328
909760
4160
ki jih same ne bi
nikoli izvedle.
15:13
What I would hope that I could further argue to you
329
913944
3201
Upam, da mi bo uspelo utemeljiti,
da govorim o začetku večceličnosti.
15:17
is that this is the invention of multicellularity.
330
917169
2600
15:19
Bacteria have been on the earth for billions of years;
331
919793
3600
Bakterije so na Zemlji že milijarde let,
15:23
humans, couple hundred thousand.
332
923417
2043
ljudje pa le nekaj sto tisoč.
15:25
So we think bacteria made the rules for how multicellular organization works.
333
925484
5509
Menimo, da so bakterije postavile pravila
za delovanje večceličnih skupnosti.
S preučevanjem bakterij
15:31
And we think by studying bacteria,
334
931017
2393
15:33
we're going to be able to have insight about multicellularity in the human body.
335
933434
4117
želimo spoznati tudi večceličnost v človeškem telesu.
15:37
So we know that the principles and the rules,
336
937575
2148
Če bi nam uspelo razvozlati
15:39
if we can figure them out in these sort of primitive organisms,
337
939747
3022
načela in pravila delovanja v teh preprostih organizmih,
bi jih lahko uporabili
15:42
the hope is that they will be applied
338
942793
1792
tudi pri človeških boleznih in delovanju.
15:44
to other human diseases and human behaviors as well.
339
944609
2804
Upam, da sem pojasnila, da bakterije
15:48
I hope that what you've learned
340
948245
1526
15:49
is that bacteria can distinguish self from other.
341
949795
2347
znajo ločiti med sebi enakimi in drugačnimi.
15:52
So by using these two molecules,
342
952166
1530
S tema dvema molekulama lahko rečejo "mi" in "oni".
15:53
they can say "me" and they can say "you."
343
953720
2259
To izražamo tudi ljudje,
15:56
And again, of course, that's what we do,
344
956003
1977
tako na molekularni
15:58
both in a molecular way, and also in an outward way,
345
958004
3462
kot na beseden način,
16:01
but I think about the molecular stuff.
346
961490
1929
a sedaj je govora o molekularnem.
16:03
This is exactly what happens in your body.
347
963443
2018
Točno to se torej dogaja v vašem telesu.
16:05
It's not like your heart cells and kidney cells get all mixed up every day,
348
965485
3595
Celice vašega srca in ledvic se ne mešajo med sabo,
saj jim na kemični način
16:09
and that's because there's all of this chemistry going on,
349
969104
2751
16:11
these molecules that say who each of these groups of cells is
350
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molekule povejo, kdo spada h kateri skupini celic
in kaj je njihova naloga.
16:15
and what their tasks should be.
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16:16
So again, we think bacteria invented that,
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Menimo, da so tak način iznašle bakterije.
Človeško telo je sicer razvilo nekoliko bolj zapletene celice,
16:20
and you've just evolved a few more bells and whistles,
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16:22
but all of the ideas are in these simple systems that we can study.
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a enak princip se vrši v teh preprostih sistemih, ki jih preučujemo.
16:26
And the final thing is, just to reiterate that there's this practical part,
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V praktičnem delu smo torej razvili molekule,
16:30
and so we've made these anti-quorum-sensing molecules
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ki ne zaznavajo celične gostote,
16:33
that are being developed as new kinds of therapeutics.
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da bi ustvarili nova zdravila.
16:36
But then, to finish with a plug for all the good and miraculous bacteria
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Da pa ne bi pozabili na vse koristne in čudovite
16:39
that live on the earth,
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bakterije na Zemlji, smo razvili tudi
16:41
we've also made pro-quorum-sensing molecules.
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molekule, ki zaznavajo celično gostoto.
16:43
So we've targeted those systems to make the molecules work better.
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Na te sisteme smo se osredotočili, da bi tako izboljšali delovanje molekul.
Ne pozabite, da je na in v vašem telesu desetkrat več
16:47
So remember, you have these 10 times or more bacterial cells
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16:50
in you or on you, keeping you healthy.
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bakterijskih celic, ki vas ohranjajo zdrave.
16:52
What we're also trying to do is to beef up the conversation
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Poleg tega smo želeli
izboljšati pogovore med bakterijami,
16:56
of the bacteria that live as mutualists with you,
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16:58
in the hopes of making you more healthy,
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ki živijo z vami v sožitju,
da bi na vaše zdravje in delovanje
17:01
making those conversations better,
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17:02
so bacteria can do things that we want them to do
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učinkovale bolje,
17:05
better than they would be on their own.
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kot bi sicer same zase.
17:08
Finally, I wanted to show you --
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Za konec vam želim še pokazati
17:10
this is my gang at Princeton, New Jersey.
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mojo družbo na Princetonu v New Jerseyu.
Vse, o čemer sem vam pripovedovala, je odkrila oseba na tej sliki.
17:13
Everything I told you about was discovered by someone in that picture.
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Upam, da se zavedate, da dejstva,
17:17
And I hope when you learn things, like about how the natural world works --
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ki se jih učite, jih preberete v časopisu
17:20
I just want to say that whenever you read something in the newspaper
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ali o njih slišite na predavanju
17:23
or you hear some talk about something ridiculous in the natural world,
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o neverjetnih naravoslovnih odkritjih,
so odkrili mladi ljudje.
17:27
it was done by a child.
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17:28
So science is done by that demographic.
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Znanost se odvija v tej starostni skupini.
Vsi od njih so stari med dvajset in trideset let
17:31
All of those people are between 20 and 30 years old,
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17:34
and they are the engine that drives scientific discovery in this country.
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in predstavljajo gonilo znanstvenih odkritij v tej državi.
Krasno je sodelovati z njimi.
17:39
And it's a really lucky demographic to work with.
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17:41
(Applause)
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Jaz se staram, ta skupina pa je vedno enakih let,
17:42
I keep getting older and older, and they're always the same age.
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zato v tem delu res izjemno uživam.
17:45
And it's just a crazy, delightful job.
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17:47
And I want to thank you for inviting me here,
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Najlepša hvala za vabilo.
17:49
it's a big treat for me to get to come to this conference.
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Zelo sem vesela sem, da sem lahko sodelovala na tej konferenci.
17:52
(Applause)
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(Aplavz)
17:57
Thanks.
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Hvala.
17:58
(Applause)
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(Aplavz)
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