Research Abstract:
Glucose sensing and signaling. Glucose fuels life, so cells have evolved numerous sophisticated mechanisms for sensing and responding to this key nutrient. This is especially apparent in the yeast S. cerevisiae, which has several highly evolved regulatory mechanisms for sensing and utilizing the widely varying amounts of glucose it encounters during its lifetime. These regulatory mechanisms determine the distinctive fermentative metabolism of yeast, a lifestyle it shares with many kinds of tumor cells, and which humans have long exploited for production of food and beverages. Our long-term goal is to understand how yeast cells sense and respond to glucose. We are studying two glucose sensing and signal transduction pathways in S. cerevisiae that affect gene expression. We are also extending our analysis of glucose sensing and signaling to the pathogenic yeast C. albicans
Comparative and Functional Genomics. A true understanding of cellular function will require knowledge of how the cell integrates many signals into its regulatory network and responds with a coordinated output. The first step toward this goal is to identify DNA sequences regulating gene expression. We have identified thousands of potential regulatory sequences in the yeast genome by their evolutionary conservation. We are developing high throughput strategies to learn which of those sequences are functional, and to connect each to the proteins that bind to them. Armed with the catalogue of regulatory proteins and their binding sites, we expect to be able to contribute to a comprehensive understanding of the regulatory network of the yeast cell.
Selected Publications:
Wang H, Johnston M, Mitra RD. Calling Cards for DNA-binding Proteins. Genome Res 2007 17:1202-1209.
Brown V, Sexton JA, Johnston M. A glucose sensor in Candida albicans. Eukaryot Cell 2006 5:1726-1737.
Johnston M and Kim J-H. Glucose as a hormone: Receptor-mediated glucose sensing in the yeast Saccharomyces cerevisiae. Biochem Soc Trans 2005 33:247-252.
Moriya H and Johnston M. Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I. Proc Natl Acad Sci USA 2004 101:1572-1577.
Cliften P, Sudarsanam P, Desikan A, et al. Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 2003 301:71-76.
Last Updated: 09/12/2007 |