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An issue of fundamental importance from evolutionary biology to medicine is the stabilization of physiology and development against genetic and environmental variation. A huge amount of molecular variation affecting signal transduction is hidden in phenotypically normal populations. This variation accounts for common heritable differences in disease predisposition and is critical for the evolution of developmental pathways. How do species remain morphologically distinct and constant over time? How can they evolve to track a changing environment?
We use standard quantitative and molecular genetics combined with emerging genome-wide approaches to study latent genetic variation in Hsp90-dependent signaling networks. Hsp90 is a chaperone for critical cell cycle and developmental regulators, including many tumor suppressors and oncogenes. Polymorphic genes that are buffered by Hsp90 in model organisms are candidate genes for human disease and targets for the evolution of development. When Drosophila Hsp90 is impaired, stunning developmental abnormalities are revealed. These depend on previously cryptic variants specific to different genetic backgrounds, and can be enriched by laboratory selection. Using these lines, we have mapped nearly a
Suzannah Rutherford has a B.A. in Biology from Reed College and a Ph.D. from the University of California, San Diego where she used Drosophila genetics to study the importance of cyclophilins in protein folding and signal transduction. This work led directly to her ongoing interest in the Hsp90 protein chaperone. Investigating interactions between Hsp90 and developmental signaling molecules in Drosophila during her postdoc in Susan Lindquist's laboratory at the University of Chicago, she discovered that Hsp90 regulates the expression of genotypic variation affecting developmental signaling and adult morphogenesis, allowing cryptic variation to accumulate in phenotypically normal populations. She developed the novel 'Hsp90 capacitor' hypothesis, under which relief from Hsp90 buffering during stress increases the expression of morphogenetic variation and evolvability. Dr. Rutherford continues her studies on the role of Hsp90 in regulating signal transduction variation and evolvability as they relate to models for cancer predisposition and evolution as an Assistant Professor in the Basic Sciences Division of the Fred Hutchinson Cancer Research Center. Dr. Rutherford is an assistant editor of BioEssays and a recipient of the 2001 Damon Runyon Cancer Research Foundation Scholar Award.
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