Research

Work in my laboratory focuses on the study of glycogen metabolism and its regulation. Glycogen is a branched polymer of glucose that functions as a store of both energy and carbon skeletons in many species ranging from mammals to bacteria. We have a longstanding interest in understanding the control of glycogen storage in the budding yeast, Saccharomyces cerevisiaeand, more recently, have expanded our work to consideration of the role of glycogen in a variety of protists of medical interest.

A. Glycogen storage in yeast

In yeast, glycogen is formed in response to nutrient limitation, such as that occurring at the approach to stationary phase in batch culture. Glycogen synthesis requires the activities of glycogenin, a self-glucosylating initiator protein, glycogen synthase, which catalyses bulk synthesis, and the branching enzyme, which introduces the branches characteristic of the mature polysaccharide. Degradation of glycogen requires the concerted action of two enzymes, phosphorylase, which liberates glucose in the form of glucose-1-phosphate from the non-reducing ends of glycogen chains, and debranching enzyme, which eliminates branch points from the molecule, facilitating phosphorylase action. These processes are illustrated schematically below.

Our current work with yeast focuses on two main areas. First, by use of a fluorescently labeled form of glycogen synthase (Gsy2-GFP) we have discovered that the subcellular distribution of the enzyme varies depending upon the glycogen content of the cell. Strikingly, we see localization of glycogen synthase to discrete subcellular structures when glycogen reserves are low and, in the complete absence of glycogen, the enzyme accumulates within the nucleus (see below)

We are beginning to address both the mechanism(s) regulating this subcellular trafficking of glycogen synthase and its significance. Secondly, two distinct isoforms of glycogen synthase are expressed by yeast cells. We are employing a combination of genetic and classical biochemical approaches to address the roles played by these different isoforms in glycogen storage.

B. Glycogen storage in early-branching eukaryotes

In a collaboration with the laboratory of Dr. Andrew Brittingham (Department of Microbiology and Immunology), we have begun a study of the role of glycogen stores in the protists Trichomonas vaginalis and Giardia intestinalis. These organisms are both of medical interest. T. vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide where G. intestinalis infection is an important cause of diarrheal illness. Both organisms have been shown to accumulate substantial quantities of glycogen at particular points during growth. Our current work addresses the kinetics of glycogen synthesis and utilization as well as the cellular mechanisms that regulate these processes.

2012 research

Work in my laboratory focuses on the study of glycogen metabolism and its regulation. Glycogen is a branched polymer of glucose that functions as a store of both energy and carbon skeletons in many species ranging from mammals to bacteria. We have a longstanding interest in understanding the control of glycogen storage in the budding yeast, Saccharomyces cerevisiae and, more recently, have expanded our work to consideration of the role of glycogen in a variety of protists of medical interest.

Publications

Wilson W.A., Henry M.K., Ewing G., Rehmann J., Canby C.A., Gray J.T., Finnerty E.P. Teach Learn Med 23:256-262. “A prematriculation intervention to improve the adjustment of students to medical school”, 2011

Wilson, W.A., Boyer, M.P., Davis, K.D., Burke, M., and Roach P.J. Can J Microbiol. 56, 408-420. “The subcellular localization of yeast glycogen synthase is dependent upon glycogen content”, 2010

Wilson, W.A., Roach P.J., Montero M., Baroja-Fernández E., Muñoz F.J., Eydallin G., Viale A.M., and Pozueta-Romero J. FEMS Microbiol Rev. 34, 952-985. “Regulation of glycogen metabolism in yeast and bacteria”, 2010

Wilson, W.A., Skurat, A.V., Probst, B., de Paoli-Roach, A.A., Roach, P.J., and Rutter, J.A., Proc. Natl. Acad. Sci. USA 102, 16596-16601. “Control of mammalian glycogen synthase by PAS kinase”. , 2005

Torija M.J., Novo M., Lemassu A., Wilson W, Roach P.J., Francois J., and Parrou J.L., FEBS Lett. 579, 3999-4004. “Glycogen synthesis in the absence of glycogenin in the yeast Saccharomyces cerevisiae”. , 2005

de Paula R.M., Wilson W.A., Roach P.J., Terenzi H.F. and Bertolini M.C., FEBS Lett. 579, 2208-2214. “Biochemical characterization of Neurospora crassa glycogenin (GNN), the self-glucosylating initiator of glycogen synthesis”. , 2005

Wilson, W.A., Wang, Z., and Roach, P.J., Biochem. Biophys. Res. Commun. 329, 161-167. “Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein kinase Pho85p” , 2005

de Paula R., Wilson, W.A., Terenzi, H.F., Roach, P.J., and Bertolini M.C., Arch. Biochem. Biophys. 435, 112–124. “GNN is a self-glucosylating protein involved in the initiation step of glycogen biosynthesis in Neurospora crassa”. , 2005

Wilson W.A., Hughes W.E., Tomamichel W. and Roach P.J., Biochem. Biophys. Res. Commun. 320, 416-423. “Increased glycogen storage in yeast results in less branched glycogen”. , 2004

Pederson, B.A., Wilson, W.A., and Roach, P.J., J. Biol. Chem. 279, 13764-13768. “Glycogen synthase sensitivity to glucose-6-P is important for controlling glycogen accumulation in Saccharomyces cerevisiae”. , 2004

Wilson, W.A., Wang, Z. and Roach, P.J., FEBS Lett. 515, 104-108. “Analysis of respiratory mutants reveals new aspects of the control of glycogen accumulation by the cyclin-dependent protein kinase Pho85p”. , 2002

Wilson, W.A., Wang, Z. and Roach, P.J., Mol. Cell Proteomics 1, 232-242. “Systematic identification of the genes affecting glycogen storage in the yeast Saccharomyces cerevisiae: implication of the vacuole as a determinant of glycogen level”. , 2002

Wang, Z., Wilson, W.A., Fujino, M.A. and Roach, P.J., FEBS Lett. 506, 277-280. “The yeast cyclins Pcl6p and Pcl7p are involved in the control of glycogen storage by the cyclin-dependent protein kinase Pho85p”. , 2001

Wang, Z., Wilson, W.A., Fujino, M.A. and Roach, P.J., Mol. Cell Biol. 21, 5742-5752. “Control of autophagy and glycogen accumulation by Snf1p, the yeast homolog of the AMP-activated protein kinase”. , 2001

Pederson, B.A., Cheng, C., Wilson, W.A. and Roach, P.J., J. Biol. Chem 275, 27753-27761. , 2000

Wilson, W.A., Mahrenholz, A.M. and Roach, P.J., Mol. Cell Biol. 19, 7020-7030. “Substrate targeting of the yeast cyclin-dependent kinase Pho85p by the cyclin Pcl10p”., 1999