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Artificial Yeast DNA Brings Science Closer to Genetic Manipulations

HOST INTRO: Synthetic biology may seem like an oxymoron. But scientists in this emerging field announced a big step in Science magazine: the recreation of one of the 16 chromosomes that make up the DNA of a humble life form: baker’s yeast. Pierre Bienaimé has more.

Saccharomyces Cerevisiae, or bakers' yeast. Creative commons courtesy of Prof. Dr. Gerhard Wanner, Munich.

Saccharomyces Cerevisiae, or bakers’ yeast. Creative commons photo.

Jef Boeke (BOO-kah) directs a team of researchers at NYU’s Langone Medical Center. They’re behind a huge milestone in synthetic biology, but Boeke makes an important disclaimer about one thing they’re not doing.

BOEKE: A lot of people think we’re creating life, and we’re not. (0:04)

Instead they’re making the language of life, DNA, from scratch.

BOEKE: We start from inanimate scraps of DNA made by a machine from chemicals, and we’re piecing those segments of DNA together into larger and larger pieces…

… Until the pieces make up an entire chromosome, which is responsible for just about any physical trait living things have. This is the first time scientists have created a chromosome artificially.

BOEKE: … and then we mix them with living yeast cells. (0:17)

Yeast is especially happy to latch onto a new chromosome, so scientists are easily able to introduce their artificial creations.

BOEKE: Essentially our synthetic DNA then swaps in for the DNA that’s already there.

About DNA. You probably know it as the famous double-helix structure, the spiral staircase. In yeast’s chromosome number 3, the one Boeke is working on, that staircase has over 300,000 steps.

But the researchers at NYU don’t put the chromosome back together just as it occurs in nature. They make changes and omissions, then test how their latest version of the synthetic chromosome behaves once it’s put back into yeast.

SOUND: Lab ambi

To do that, you need lots of good old, natural yeast. So we go next door, to the laboratory that shares a wall with his office.

SOUND: Rotating device

BOEKE: What you’re hearing is the sound of yeast growing in a rotating device, that’s rotating tubes of yeast growing in liquid culture. (0:11)

 The rotating device looks like a fridge from the outside. It’s got the same kind of door… SOUND: Rotating device door closing

And it keeps the yeast at a comfortable 30 degrees centigrade, warmer than room temperature.

A bit more high-tech is the centrifuge…

BOEKE: We’re tightening the lid of the centrifuge here.

SOUND: Centrifuge top being screwed shut.

This thing spins vials of yeast at a rate of up to 15,000 revolutions per minute.

BOEKE: It’s basically just spinning little tubes of liquid around to get the liquid to the bottom of the tube, or do what’s called precipitation.

SOUND: Centrifuge spinning

That spinning isolates the yeast’s DNA, separating it from other stuff that remains at the bottom of the tube.

SOUND: Centrifuge slowing to a stop

 Back in his office, I ask Boeke about the grand implications of tailoring the natural world’s genes.

BOEKE: You’re probably trying to get me to say something about Jurassic Park. We don’t have any plans to do that. (0:06)

 Boeke acknowledges that de-extinction—bringing back a dinosaur, for example—might be possible using these techniques. But it’s more likely that the research done here will allow scientists to improve upon plants…

BOEKE: … with fantastic new traits: disease resistance, improved yields, improved nutritional value.

 This is made possible by using yeast as a lab of its own. Chromosomes can be built within living yeast, but they don’t have to stay there.

BOEKE: That’s definitely something I think you’re going to be seeing in the future: designer chromosomes built in yeast and then transferred for example into plants, or animals, or even humans for gene therapy.

Boeke’s lab isn’t alone in working towards such applications. About a dozen universities and institutes are each tackling their own yeast chromosome, collaborating to eventually have the entire genome synthesized. One of them is in London.

ELLIS: I’m Dr. Tom Ellis from Imperial College London from the Center of Synthetic Biology and Innovation.

Ellis’ group is about a third of the way to synthesizing chromosome 11. Synthetic biology, he says, could lead to powerful new medicines.

 ELLIS: What excites me most are things like the production of antibiotics. We know that there’s a lack of those right now, and a lack of a pipeline of new ones coming.

Basically, bacteria are outsmarting our medicines by evolving resistance to them. But since antibiotics are often made by life forms like fungi and soil bacteria, Ellis says scientists could eventually take that trait and lend it to other creatures.

ELLIS: We’ll be effectively using the synthetic genome as a chassis to give DNA from around nature to the yeast to equip it with the ability to outcompete bacteria.

Tougher plants and tougher medicine are only some of the applications synthetic biology might yield. To get there, Boeke and his international partners are hoping to have all of yeast’s chromosomes synthesized within four years.

Pierre Bienaimé, Columbia Radio News.

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