The Rusche Lab studies chromatin and its impact on gene expression and chromosome function. We also study how protein functions shift over evolutionary time through mechanisms including gene duplication and rewiring of transcriptional circuits. In our studies, we gain an evolutionary perspective by comparing multiple yeast species, taking advantage of the genome editing and comparative genomic approaches available for these species.
One arm of our research program focuses on Sir2 proteins (sirtuins), which deacetylate histones to repress transcription. Because sirtuins require NAD+ for activity, they are thought to link the processes they regulate with nutrient availability. We are investigating how the functions of yeast sirtuins have shifted over the course of evolution to enable species to develop distinct responses to low NAD+ stress.
Another arm of our research focuses on the nucleosome-binding protein Sir3, which partners with Sir2 to form heterochromatin. We are reconstructing the steps by which Sir3 evolved from the conserved replication protein Orc1 through gene duplication, subfunctionalization, and specialization.