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O'Shea Lab > People >Bin He

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Within and between species variation in yeast stress response
Bin He binhe@fas.harvard.edu

Both genetic and non-genetic differences contribute to phenotypic variation within and between species, which provides the raw materials for natural selection to act and contribute to the diversities we observe on our planet. My broad interest is in understanding how genetic variation underlie the phenotypic differences. Furthermore, I would like to use a model system like yeast to elucidate the molecular (biochemical and biophysical) mechanisms by which genotypic variation influences the phenotype, and the epistatic interactions between genotypic variations.

My current project involves the evolution of a stress-response signaling pathway. In S. cerevisiae , PHO4 needs to interact with PHO2 to illicit full response during phosphate starvation. This lab has previously found that in Candida glabrata, a species more closely related to the Saccharomyces than to Candida albican, has lost this interaction. Together with Xu, a graduate student in the lab, we are investigating the sequence determinants and functional consequences for this change. We are testing several hypotheses about the evolutionary mechanisms for such a change. As molecular interactions in signaling pathways are ubiquitous, this study may serve as a model for understanding how the interactions may be gained and lost during evolution and its likely consequences at the genomic level.

In the long term, I would like to use stress-response as a model to elucidate the following questions: (1) What genetic pathways may harbor variation that can lead to phenotypic differences? How do they compare to the core pathways identified? (2) How widespread is epistasis in the genetic architecture? These two questions will lead me to a more systematic view of the genetic determinants for a complex trait, such as stress-response, which I believe is essential for understanding such questions as the genetic basis for complex disease.


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