Howard Hughes Medical Institute 2010 Annual Report

Thom Kaufman, director of the Bloomington Drosophila Stock Center at Indiana University

Thom Kaufman, director of the Bloomington Drosophila Stock Center at Indiana University

Kaufman on the Immense Value of the Tiny Fly

As director of the Bloomington Drosophila Stock Center (BDSC) at Indiana University, Thom Kaufman knows something about the value of scale.

The facility houses 30,000 genetically distinct fruit fly strains and is a resource for the worldwide community of scientists who study the fruit fly, Drosophila melanogaster, as a model organism for understanding disease, basic biology, and behavior. Thanks to a new grant from HHMI, the BDSC is poised to renovate and expand the facility so it can more than double its capacity.

Q: How has Drosophila changed what’s possible in modern science?

A: When I was a grad student, you knew what genes were because you could map them. And you knew that a gene produced a phenotype because you could observe the change. But you didn’t know how that gene resulted in that phenotype. It was a black box. But that black box has been opened. We’ve sequenced the fly genome, which was once beyond imagining. And we can do transgenesis—take a gene, have your way with it in an Eppendorf tube, and then put it back into the fly. That allows you to do all sorts of wonderful things.

Q: What can you do with 70,000 strains that you could not do with 30,000?

A: The fly community is full of hard-working, inventive people who keep building new tools. And the tool construction has gone on at a logarithmic rate. With 30,000 stocks, you can get into the genome of the fly, tinker with it, rearrange it to what you want to make it do, and then find out what the consequences are in the animal.

Now we want double that number. The reason is that it will dramatically expand our ability to apply new technologies to genetic, developmental, and behavioral analysis. You can go in and tinker with specific nerve cells in the central nervous system—the technology is that fine-grained!

We know now that the fly’s genome is not all that terribly different from our own, and there are human disease models in the fly. You can do things cheaply and be pointed in the right direction before you go into the more complicated mammalian systems. In the end, the more tools you have, and you can think of a fly strain as a tool, the more likely you are to ameliorate human suffering.

Q: What are some of the more fascinating strains housed at the BDSC?

A: I’ve loved flies since I first met them 40 years ago. For years, I worked on strains in which one organ is turned into something else—for example, we can turn the antennae into legs.

There are mutations called shibiri, which is Japanese for paralyzed. At 22 degrees Celsius, the flies are perfectly fine—running around, flying, doing all the things that flies do—but if you shift to 29 degrees, they’re paralyzed. If you shift back to 22 degrees, they get up and fly away. There are bang-sensitive mutations, so if you knock a vial of flies against a desk or stick them in a vortex and shake them up, it knocks them out. There’s a mutant called cheap date, which is incredibly sensitive to alcohol vapors.

Q: What are the biggest outstanding questions in fly genetics?

A: One of the big questions in evolution is how do you take the same toolbox of genes and make such different animals? Clearly we have a similar set of proteins to the fruit fly, but I don’t know a fruit fly that can play chess. Then again, I don’t know any humans who can fly. So this is a problem. I don’t know if anybody anticipated this incredible genetic similarity across the entire animal kingdom. It’s stunning.

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Photo Credit: Courtesy of Indiana University