Glucose sensing and signaling in yeasts
Glucose fuels life. It is the preferred carbon and energy source of most cells and the only source for some cells (e.g., brain cells). Because of this, cells have evolved sophisticated mechanisms for sensing glucose and responding to it appropriately. 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 (bread) and my favorite beverage (beer). Our long-term goal is to understand how yeast cells sense and respond to glucose.
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 coor dinated output. An important piece of this puzzle is identification of the proteins that regulate gene expression and the DNA sequences they recognize. We can identify potential regulatory sequences by comparative genomics and we can test these hypotheses with functional genomics. We are developing and implementing high throughput genetic and biochemical strategies for this purpose. 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 this reference eukaryotic cell. This project offers opportunities to couple training in computational biology with experimental work.
Representative Publications:
Giaever G, 72 others, JOHNSTON M: Functional Profiling of the S. cerevisiae Genome. Nature 2002; 418:387-391. PMID: 12140549
Cliften P, Sudarsanam P, Desikan A, Fulton L, Fulton B, Majors J, Waterston R, Cohen BA, JOHNSTON M: Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting, Science 2003; 301:71-76. PMID: 12775844
Moriya H, JOHNSTON M: Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I. Proc. Natl. Acad. Sci. USA. 2004; Feb 10; 101(6):1572-7.
PMID: 14755054
Polish J, Kim J-H and JOHNSTON M: How the Rgt1 transcription factor of S. cerevisiae is regulated by glucose. Genetics 2005; 169(2):583-594. PMID: 15489524
Kim J-H, Brachet V, Moriya H, and JOHNSTON M: Integration of transcriptional and post-translational regulation in a glucose signal transduction pathway in Saccharomyces cerevisiae. Eukaryotic Cell 2006; 5:167-73. PMID: 16400179
Cliften PF, Fulton RS, Wilson RK, and JOHNSTON M: After the duplication: gene loss and adaptation in Saccharomyces genomes. Genetics 2006; 172:863-872. PMID: 16322519
Ho S-W, Jona G, Chen CT, JOHNSTON M, Snyder M: Linking DNA-binding proteins to their recognition sequences by using protein microarrays. Proc Natl Acad Sci U S A. 2006; 103:9940-5. PMID: 16785442
Brown V, Sexton JA, JOHNSTON M: A glucose sensor in Candida albicans. Eukaryot Cell. 2006; 5:1726-37. PMID: 17030998
Kim J-H, JOHNSTON M: Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae.. J Biol Chem. 2006; 281:26144-9.
PMID: 16844691
Wang H, JOHNSTON M, Mitra RD: Calling Cards for DNA-binding Proteins. Genome Res. 2007; 17:1202-1209. PMID: 17623806
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