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Regeneration of nerves -

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Robyn Williams: This is The Science Show where small is very big, like the nano work of Professor
Yanik at MIT. He's Turkish, by the way, putting a nano worm in a chip to operate.

I'm rather surprised by the fact that you, an electrical engineer, are working on the nervous
system of an animal, so you're doing biological work. How did that come to be?

Mehmet Fatih Yanik: That was a long-standing interest I had in biology. I didn't want to do biology
the usual way it is done because I thought there are enough people doing it, and I tried to bring
new technologies to solve some of the challenging questions.

Robyn Williams: These new technologies are really astonishing. I've just been to your lab and I've
seen the way that you have a kind of chip into which you put the nematode worm, these tiny, tiny
microscopic worms, which is difficult enough in the first place, but then you can use various
techniques to have a kind of glowing nervous system, you can actually see the nervous system
illuminated in a kind of bright green, you can see the wiring. And then you can use tiny pulses of
laser light in incredibly short bursts to cut the nervous system and then watch it regenerate.
That's an amazing process, getting it really down to the nano scale. Was it very difficult to
develop this technology?

Mehmet Fatih Yanik: To be able to manipulate the animals we developed microchip technologies. These
are used for the fabrication of the chips that we use in our computers but they are modified
versions of them, and to be able to cut individual nerve processes at such a high precision we
basically applied femtosecond laser pulses.

Robyn Williams: Femtosecond is unbelievably fast, isn't it. It's a zillion billionth of a second.

Mehmet Fatih Yanik: It's true, it's about 10-15 second.

Robyn Williams: And you can actually cut a chromosome, you're actually operating, doing surgery at
the molecular level.

Mehmet Fatih Yanik: With this technology we can cut individual nano scale connections that connect
individual neurons to each of them. For example, we can nick out synaptic junctions, we can nick
out axonal connections. These are connections that neurons use to communicate with each other, and
we can study various questions. We can, for example, ask the question how they regenerate after
such a physical injury, or we can ask the question how the nervous system works by basically taking
out pieces of a lego then you can start decrypting how it works.

Robyn Williams: And when the nematode worms' cut nervous system regenerates, does it do so in a
short time?

Mehmet Fatih Yanik: Yes, it is amazingly short, it's about in 12 hours, and that is very powerful
because with this technique we can study neural regeneration on a large scale very rapidly. The
reason it regenerates so fast is not because its biology is much different than ours but because
the distances they need to generate is a lot shorter than our neural system.

Robyn Williams: I see, and so it regenerates automatically, it rewires automatically, you don't
have to do anything.

Mehmet Fatih Yanik: We don't have to do anything, but the nice thing is it neither generates
perfectly or it doesn't generate at all, it's partial. So what we are trying to do now is trying to
understand whether we can enhance its regeneration or discover factors that inhibit its
regeneration.

Robyn Williams: I see, the big puzzle was that if you want to study regeneration in a nervous
system...and I see that you had a picture of Christopher Reeve, Superman, and the figures of the
number of people who...I think it's 400,000 people in the United States who are injured in this way
and they've got nervous systems which doesn't work, they're paraplegic or quadriplegic, but our
nervous systems are different. They're bigger, they're insulated with myelin, so you've got a
different kind, you've also got a bigger wire to look at. Do you think that what you find in the
nematode worm will be enough to give you clues about how our system works?

Mehmet Fatih Yanik: That's an excellent question. First of all, like you mentioned, C. elegans
doesn't have this myelin sheath, it has some sort of sheathing but it's not like the myelin that
our system has. But there are several questions that we haven't been able to discover in high
organisms. For example, we don't yet understand the full mechanism of intrinsic factors that
control neural regeneration, and we can study those questions very easily in C. elegans . The other
things that our lab is doing, we are also developing high-throughput screening technologies using
microchips again, by using human embryonic stem cell derived neurons. This way we are basically
able to transfer our findings in C. elegans and test them very rapidly on a human tissue very
quickly.

Robyn Williams: I must say, C. elegans is the good Latin name of the worm, isn't it?

Mehmet Fatih Yanik: Yes.

Robyn Williams: You've just published the paper in The Proceedings of the Academy of Science in
America, what's the next stage? Having done so much with the worm, how are you going to enhance
this work?

Mehmet Fatih Yanik: Our first publication was a demonstration of the technology. The next stages,
we are going to start performing very large scale screens. So we are going to basically turn off
every single gene one by one and ask how neural regeneration is affected by different genes. Then
we are also going to perform similar screens using drug libraries, for instance. With this
technology we will be able to for the first time on an animal we will be able to perform a screen
that involves hundreds of thousands or even millions of compounds very rapidly.

Robyn Williams: Just imagine a picture, because genetic systems, they're maps of fuses turning
things on an off...I should imagine that if you find ways in which you can turn on and off
particular genes that connect to the nervous system in this nematode worm and also understand the
chemical systems involved you could then look at other animals like us.

Mehmet Fatih Yanik: That's correct, that's exactly what we are going to do next. So, as you say,
once we discover something in C. elegans , which is actually an animal model, very rapidly then we
can test those candidates on this human tissue very quickly.

Robyn Williams: It's very exciting. Congratulations.

Mehmet Fatih Yanik: Thank you.

Robyn Williams: It really is incredible technology; nano surgery on a microscopic worm. Mehmet
Yanik is a professor of electrical engineering at MIT.