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INTERVIEW //

Origin of Life: Back to the Beginning

Nobel Prize winner Jack Szostak wanders off the beaten path to figure out how cellular life got started.

By Lauren Ware // The MGH Research Issue 2011
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jack szostak

Denise Bosco for Proto

Jack Szostak, a researcher in the department of molecular biology at MGH, shared the 2009 Nobel Prize for the discovery of how telomeres, structures located at the ends of chromosomes, protect the chromosomes from damage. Today he is studying how the building blocks of life transformed themselves from a handful of chemicals into primitive cells that can grow, divide, replicate their genetic material and evolve.

Q: You haven’t worked on telomeres for about 20 years. Why did you move on?

A: Once we discovered the connection between telomeres and senescence in yeast, the next step would have been to look at telomeres in mice and in humans. A lot of scientists were going to do that. So I decided to find another area in which there were still interesting questions but not so many people working on them.

Q: Is that how you got interested in studying the origin of life?

A: In the mid-1980s, I started working on ribozymes, enzymes made of RNA, that were then an exciting recent discovery. We spent most of the 1990s looking at various methods of directed evolution, by which we kind of force the RNA to evolve using specialized laboratory methods. That got me more and more focused on questions of how life got started on the early earth, and thinking about what simple, primitive cells might have looked like. During the past 10 years, that work has evolved into the whole protocell project.

Q: What is the protocell project, exactly?

A: We are trying to discover how the important chemical building blocks of life—including nucleotides, which make up DNA and RNA, and fatty acids, which make up the cell membrane—can interact with each other and make very simple cells that grow, divide and, most important, evolve in a Darwinian sense. Understanding how that might have happened could give us insight into the origin of life on earth. We’re learning a lot about primitive cell membranes, how we can make tiny sacs formed by the membranes grow and divide using just physics and chemistry—we shake them gently and they break apart into smaller sacs. These sacs, or vesicles, have no evolved biological machinery, no enzymes, no cytoskeleton, nothing that resembles a modern cell. We are assuming all of that came later.

Q: What has been the biggest surprise?

A: When we started to study how protocells actually grow and divide, we were shocked when we looked at them in the microscope. We saw how initially spherical vesicles grow into these long, filamentous shapes, which are then very easy to divide just by shaking gently. It’s a very simple process, but it was completely unanticipated.

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Video: Back to the Beginning

jack szostak

Jack Szostak discusses how basic research begets transformative discoveries.

Telomeres: DNA Unlaced

Nobel Prize-winning work by Jack Szostak, Carol Greider and Elizabeth Blackburn has shown that telomeres do damage control, preserving DNA and slowing aging. What happens if we extend their expiration date?

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