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Tracking Genes in Cell Morphology

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  • Title: Assistant Professor, University of California, San Diego
  • Education: PhD, Stanford School of Medicine, 2001
  • Recommended by: Steve Briggs

In her three-year-old lab at the University of California, San Diego, Amy Kiger is getting cell morphology studies on their feet. Her lab is undertaking a lot — studies on cell morphology regulation in vivo and in cultures — but her group is up for the challenge. “We’re working on problems involved in cell shape changes, and that’s a really dramatic example of coordinating cell spatial information,” says Kiger. “Really, that’s the underlying theme of my lab.”

Using RNAi screens and microarray data, Kiger is looking for the genes involved in the complex decision-making processes that ultimately give cells their shape — she induces a particular cell shape and then looks for functional changes. Kiger focuses on a genetic approach to studying lipid-mediated signaling events; she was, after all, trained as a developmental geneticist. “We think the genetic approach is really less well tapped,” Kiger says. Since lipids can’t be knocked out, she directs her energies toward knocking out or down the phosphatases or kinases that modify the lipids. Lipids, especially phosphatidylinositol phosphate lipids, mediate events including cytoskeletal rearrangements and membrane trafficking, and they can also be a protein localization signal. “So it’s kind of like, what haven’t they been implicated in?” she jokes.

Kiger performs these screens and microarray studies together with her in vivo developmental genetic studies. “I see the advantage of working in parallel between the two systems, cells and culture, where we can do the systematic screens, combination screens, and then take the cell-based insights and try to really understand that cell biology in the context of tissues,” she says.

Setting up her own lab has been challenging and exciting, especially in planning experiments and going after them at a sustainable pace. Kiger wants to use genetics to infer pathway-mediating response, as well as to visualize where in the cells the lipids are located. “It can be challenging. I want to do it all at once,” she says.

Some of that ambition stems from the scientists who had the most influence on Kiger’s career. She cites Stanford’s Margaret Fuller and Harvard’s Norbert Perrimon, both advisors over the years, as particularly instrumental in shaping her scientific approach.

Looking ahead

The next few years will be busy. It’s time, says Kiger, to put into practice all the new tricks, play a little bit of catch up, and ramp up throughput. “There’s still a lot of work-up as far as the analysis, the follow-up and really, truly integrating it with other genomic information,” she says. “It’s just catching up with our ideas.”

Publications of note

As a postdoc at Harvard Medical School, Kiger worked with her colleagues to develop a way to adapt RNAi to genetically screen Drosophila cultures, followed by using automated fluorescence microscopy to detect morphological phenotypes. They found phenotypes for 160 genes, a third of which had not been characterized in vivo, according to their 2003 Journal of Biology article. “We were greeted with a lot of skepticism when we talked about [wanting] to look at morphology for morphology’s sake. It is regulated in the cytoskeleton and we can disrupt it in very characteristic ways,” says Kiger. “This has been very successful for in vivo screens, so if we apply this to cell-based screens we’re going to gain some insights — a nice beginning to the types of things we can do.”

How to succeed in science

To succeed in science, Kiger says researchers need a combination of patience and ambition. Also important are perseverance, creativity, hard work, and the ability to ask the right questions. “Obviously, a bit of luck doesn’t hurt,” she adds.

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