Glucose Sensing and Signaling
Glucose fuels life, and organisms have evolved sophisticated mechanisms for sensing
and responding to this key nutrient. This is especially apparent in the yeast S.
cerevisiae, which has several sophisticated mechanisms for sensing and utilizing the
widely varying amounts of glucose it encounters during its lifetime. We are focused on a
novel glucose signal transduction pathway that begins with glucose sensors in the
membrane and ends at a transcription factor in the nucleus. We can trace the glucose
signal from the cell surface all
the way to the nucleus, and we are poised to come to a
true understanding of how this
novel signal transduction
pathway works. We are also
studying the evolution and
systems biology of this
signaling pathway. Our
studies of glucose sensing
and signaling extend to the
pathogenic yeast C. albicans
because it provides an
informative evolutionary
comparison, and because this central signaling pathway may
provide therapeutic targets.
Functional Genomics
We are applying Next Generation DNA sequencing technology to address questions in evolutionary and developmental biology. One project is to use the novel “Calling Card” method
we developed, in which we endow transcription factors with the ability to leave a mark in the genome wherever they bind. We intend to use this method to trace transcription factor binding
through the differentiation process of stem cells. Another project is to use ChIP-Seq and related approaches to learn how regulatory networks evolve. We continue to find new ways to apply this emerging technology to our projects, so I foresee this part of the lab expanding.
Representative Publications:
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
Brown V, Sabina J, JOHNSTON M: Specialized Sugar Sensing in Diverse Fungi. Curr. Biol. 2009; 19:436-441. PMID: 19249212
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