My research interests focus on understanding how genes are regulated. All of our cells have the same genes, but our liver cells are different from our heart cells which are different from our skin cells. The difference is in which genes are turned on and which genes are turned off. Organisms are also able to adapt to changing environmental conditions by altering gene regulation, and several diseases are known to result from the misregulation of genes.
I am also interested in the molecular mechanisms by which organisms respond to nutrient limitation. Part of this response has been well-characterized, but there is still a lot to learn. A small molecule called Rapamycin has been identified that inhibits the nutrient-sensing pathway and so makes cells “think” that they are starving. Treating cells with rapamycin leads to many responses favoring the reuse of nutrients (for example, breaking down non-essential proteins to reuse the amino acids). It also leads to a rapid and dramatic change in gene regulation.
I have combined these interests by studying the molecular mechanisms that lead to altered gene regulation following nutrient limitation. The yeast Saccharomyces cerevisiae is a single-celled eukaryote. This yeast has similar mechanisms for regulating gene expression to those used by humans, but they are much simpler. Yeast are also easy to grow, have a short generation time, and can be easily genetically manipulated.
One way that both yeast and humans regulate gene expression is by acetylating and deacetylating lysine residues on histone proteins (the proteins that DNA is wrapped around in eukaryotic cells). The acetyl groups are attached by histone acetyltransferases (HATs) and taken off by histone deacetylases (HDACs). I have identified a yeast HDAC, Rpd3p, that is required for both the activation and repression of many genes. I have shown that Rpd3p becomes bound to the promoters of many genes following treatment with rapamycin.
My current research focuses on understanding, at the molecular level, how Rpd3p becomes bound to these gene promoters following rapamycin treatment.