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  • [Intro Music]

  • [Applause]

  • What I am going to show you are the astonishing molecular machines that create the living

  • fabric of your body. Now, molecules are really, really tiny, and by tiny I mean really.

  • They're smaller than the wave length of light. We have no way to directly observe them,

  • but through science we do have a fairly good idea of what's going on down at the molecular scale.

  • But, so what we can do is actually tell you about the molecules but we don't really have

  • a direct way of showing you the molecules. One way around this is to draw pictures,

  • and this idea is actually nothing new, scientists have always created pictures as part

  • of their thinking and discovery process. They draw pictures of what they are observing with their

  • eyes, through technology like telescopes and microscopes, and also what they are thinking

  • about in their minds. I've picked two well known examples because they both...

  • they're very well known for expressing science through art, and I start with Galileo, who used

  • the world's first telescope to look at the moon, and he transformed our understanding of the moon.

  • The perception of the 17th century was the moon was a perfect heavenly sphere, but

  • what Galileo saw was a rocky, barren world, which he expressed through his water colour painting.

  • Another scientist with very big ideas, the superstar of biology, is Charles Darwin,

  • with this famous entry in his note book. He begins in the top left hand corner with I think,

  • and then sketches out the first tree of life, which is his perception of how all the species,

  • all living things on Earth, are connected through evolutionary history, the origin of

  • species through natural selection, and divergence from an ancestral population.

  • Even as a scientist, I used to go to lectures by molecular biologists and find them completely

  • incomprehensible, with all the fancy technical language and jargon that they would use in

  • describing their work, until I encountered the artworks of David Goodsell, who was a

  • molecular biologist at the Scripps Institute. And his pictures are all, everything is accurate,

  • it's all to scale, and his work illuminated for me what the molecular world inside us

  • is like. So in the top left hand corner you've got this yellow-green area, this is a transaction

  • through blood. The yellow-green areas is the fluids of blood which is mostly water,

  • but it is also antibodies, sugars, hormones, that kind of thing, and the red region is a slice

  • into a red blood cell, and those red molecules are haemoglobin, they are actually red, that's

  • what gives blood its colour, and haemoglobin acts as a molecular sponge to soak up the

  • oxygen in your lungs and then carry it to other parts of the body. I was very much inspired

  • by this image many years ago, and I wondered whether we could use computer graphics to

  • represent the molecular world. What would it look like, and that's how I really began.

  • So, um, let's begin.

  • This is DNA in its classic double helix form, and it's from X-ray crystallography, so it's

  • an accurate model of DNA. If we unwind the double helix and unzip the two strands, you

  • see these things that look like teeth, those are the letters of genetic code, the 25,000

  • genes you've got written in your DNA. This is what they typically talk about,

  • the genetic code, this is what they are talking about. But I want to talk about a different aspect

  • of DNA science, and that is the physical nature of DNA, and it's these two strands that run

  • in opposite directions, for reasons I can't go into right now, but they physically run

  • in opposite directions, which creates a number of complications for your living cells, as

  • you're about to see, most particularly when DNA is being copied. And so, what I am about

  • to show you is an accurate representation of the actual DNA replication machine that's

  • occurring right now inside your body, as at least 2002 biology. So DNA is entering the

  • production line from the left hand side, and it hits this collection, this miniature biochemical

  • machines that are pulling apart the DNA strands and making an exact copy. So DNA comes in

  • and hits this, this blue donut shaped structure, and it's ripped apart into its two strands.

  • One strand can be copied directly, and it can be seen spooling off, down to the bottom there,

  • but things aren't so simple for the other strand, because it must be copied backwards,

  • so it's thrown out repeatedly in these loops and copied, one section at a time, creating

  • two new DNA molecules. Now, you have billions of this machine, right now, whirring away

  • inside you, copying your DNA with exquisite fidelity. It's an accurate representation

  • and it is pretty much at the correct speed for what is occurring inside you.

  • I've left out error correction and a bunch of other things.

  • [Laughter]

  • This was work from a number of years ago...

  • [Applause]

  • Thank you, this was work from a number of years ago, but what I show you next is updated

  • science, it's updated technology. So again, we begin with DNA, and it's jiggling, wiggling

  • there because of the surrounding super molecules, which I've stripped away so you can see something.

  • DNA is about 2 nanometres across, which is really quite tiny, but in each one of your cells,

  • each strand of DNA is about 30-40 million nanometres long, so to keep the DNA organised,

  • to keep, ah, regulated access to the genetic code, it's wrapped around these purple proteins,

  • I've labelled them purple here, it's packaged up and bundled up. This is, all of this field

  • of view, is a single strand of DNA. This huge package of DNA is called a chromosome, and

  • I'll come back to chromosomes in a minute. We're pulling out, we're zooming out, out

  • through a nuclear pore, which is sort of the gateway to this compartment which holds all

  • the DNA called the nucleus. All of this field of view is about a semester's worth of biology

  • and I've got seven minutes, so we're not going to be able to do that today.

  • No, I'm being told no.

  • [Laughter]

  • This is the way a living cell looks down a light microscope, and it's been filmed under

  • time lapse which is why you can see it moving. The nuclear envelope breaks down, the sausage

  • shaped things are the chromosomes, and we'll focus on them. They go through this very striking

  • motion that is focused on these little red spots. When the cell feels like it's ready

  • to go, it rips apart the chromosome. One set of DNA goes to one side, the other side gets

  • the other set of DNA, identical copies of DNA, and then the cell splits down the middle.

  • And again, you have billions of cells undergoing this process right now inside of you.

  • Now we're going to rewind and just focus on the chromosomes, and look at its structure and

  • describe it. So again, here we are at that equator moment. The chromosomes line up and

  • if we isolate just one chromosome, we're going to pull it out and have a look at its structure.

  • So this is one of the biggest molecular structures that you have, well at least as

  • far as we've discovered so far, inside of us. So this is a single chromosome, and you

  • have two strands of DNA in each chromosome, one is bundled up into one sausage, the other

  • strand is bundled up into the other sausage. These things that look like whiskers, that

  • are sticking out from either side are the dynamic scaffold in the cell, they're called

  • microtubules but their name is not so important, but what we're going to focus on is this

  • red region, I've labelled it red here, and it's the interface between the dynamic scaffolding

  • and the chromosomes. It is obviously central to the movement of the chromosomes. We have

  • no idea, really, as to how it's achieving that movement. We've been studying this thing

  • they call the kinetochore for over a hundred years, with intense study, and we are still

  • just beginning to discover what it's all about. It is made up of about 200 different

  • types of proteins, thousands of proteins in total. It is a signal broadcasting system.

  • It broadcasts through chemical signals, telling the rest of the cell when it's ready,

  • when it feels that everything is aligned and ready to go, for the separation of the chromosomes.

  • It is able to couple onto the growing and shrinking microtubules. It's transiently,

  • it's involved with the growing of the microtubules, and it's able to transiently couple onto them.

  • It's also a tension sensing system. It is able to feel when the cell is ready,

  • when the chromosome is correctly positioned. It is turning green here because it feels

  • that everything is just right, and you'll see there this one little last bit that's

  • just remaining red, and it's walked away, down the microtubules. That is the signal

  • broadcasting system sending out the stop signal and it's walked away, it's that mechanical.

  • It's molecular clockwork, it's how you work at the molecular scale. So, with a little

  • bit of molecular eye candy...

  • [Laughter]

  • We've got kinesins which are the orange ones, they're little molecular courier molecules

  • walking one way, and here are the dynein, they're carrying that red broadcasting system,

  • and they've got their long legs so they can step around obstacles and so on. So again,

  • this is all derived accurately from the science. The problem is we can't show it to you any other way.

  • Exploring at the frontier of science, at the frontier of human understanding, is mind blowing.

  • Discovering this stuff is certainly a pleasurable incentive to work in science, but most medical

  • researchers, this is, discovering this stuff is just steps along the path to the big goals

  • which are to eradicate disease, to alleviate the suffering and the misery that disease causes,

  • and to lift people out of poverty, and so with my remaining time, my four minutes, 0:09:32.090:09:38.370 I'm going to show you, introduce to one of the most devastating and economically important

  • diseases, which inflict hundreds of millions of people each year. So again, actually sound,

  • thank you.

  • [Background insect and nature sounds]

  • This parasite is an ancient organism. It has been with us since before we were human.

  • Famous victims include Alexander the Great, Genghis Khan and George Washington. This is the neck

  • of a sleeping child just after the sun has set, and it's feeding time for mosquitoes,

  • it's dinner time.

  • [Mosquito noises]

  • This mosquito is infected with the malaria parasite. Now mosquitoes are usually vegetarian,

  • they drink honey dew, nectar, fruit juices, that that kind of thing, only a pregnant female will

  • bite humans, seeking nutrients from blood to nourish her developing eggs.

  • [Rainforest noises]

  • During the bite she injects saliva, to stop the blood from clotting, and to lubricate

  • the wound. Because she is infected with malaria, she, her saliva also contains the malaria

  • parasite, so it rides in during the bite. The parasite then exits the wound and seeks

  • out a blood vessel, and uses the blood vessel, the circulatory system, as a massive freeway,

  • heading for its first target, the core of your body's blood filter system, the liver.

  • Within two minutes of the bite, the malaria parasites arrive at the liver, and sensing

  • its arrival then looks for an exit from the blood stream, and this is where malaria is

  • particularly devious because it uses the very type of immune cell that is there, resident

  • in the blood stream, the immune cell is supposed to remove foreign invaders like bacteria and

  • parasites, but somehow, we are not quite sure how, malaria uses a backdoor entry into

  • the liver tissue. Here is that immune cell. Malaria leaves the blood stream, and infects

  • a liver cell, killing one or more liver cells on its way. So again this is within a couple

  • of minutes of the mosquito bite. Once it's infected a liver cell, it takes the next five

  • or six days. It incubates; it copies its DNA over and over again, creating thousands of

  • new parasites, so it's this delay of about a week since you've had the mosquito bite

  • before malaria symptoms start to appear. The malaria also transforms its physical nature,

  • it's heading for a new target. That next target is your red blood cells.

  • [Zooming noises of red blood cells and parasites]

  • As part of its transformation, the malaria coats itself with a coating of molecular hairs

  • that act like a, like a Velcro to stick onto red blood cells, um, to the outer surface,

  • and then they reorient themselves and penetrate inside the red blood cell. This happens within

  • 30 seconds of leaving the liver. This is actually an area of intense study, if we can stop this

  • process, we could, we could create a vaccine for malaria. Once it's inside the red blood

  • cell it can hide from your body's immune system. It then, over the next few days, devours

  • the contents of the infected cell, and creates more parasites.

  • [Underwater sounds]

  • It also changes the nature of the red blood cell and makes it sticky, so it sticks onto

  • red blood, ah, blood vessel walls. This gives the parasite enough time to incubate and grow.

  • Once it's ready it then bursts out of the red blood cell, spreading malaria throughout

  • the blood stream. Malaria victims suffer fever, loss of blood, convulsions, brain damage and coma.

  • Countless millions have been killed by it. This year between two and three hundred

  • million people will be struck down with malaria. Most people who die from the disease are pregnant

  • women and children under the age of 5. Thank you.

  • [Applause]

[Intro Music]

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B2 US dna malaria blood molecular red blood chromosome

Drew Berry - Astonishing Molecular Machines

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    呼喵~ posted on 2015/05/04
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