We are interested in analyzing how local amino acid sequence in the substrate, Pcl binding to substrate and intracellular localization combine to determine in vivo substrates. Ultimately, we want to link Pcl biochemistry to cellular function. Genomic approaches to study glycogen metabolism and signaling. Using the yeast genome deletion set, we have screened the genome for genes that glycogen affect glycogen storage. We are now involved in data analysis and are planning for future related screens.
Proteomic approaches to analyze protein kinase specificity.
We are interested in developing methods to assess changes in the phosphorylation pattern of proteins from cells lacking or over-expressing a given protein kinase or, in the case of Pho85p, a given cyclin partner. Autophagy and glycogen metabolism. Genetic screens have revealed that the process of autophagy is necessary for the maintenance of glycogen once it is synthesized. We are pursuing the mechanistic links, since some regulators, Snf1p and Pho85p, may control both glycogen metabolism and autophagy. These animal models will be used to address the question of the physiological role and the regulation of the phosphatase both in cardiac and skeletal muscle.