Institute of Genetics and Selection of Industrial Microorganisms,
Postdoctoral Research Scientist (1993-1998)
Columbia University, New York, NY
Associate Research Scientist (1998-2004)
Columbia University, New York, NY
Office: Lapham 442
Research InterestsWe are investigating the regulatory mechanisms that control growth and development in Saccharomyces cerevisiae (baker's yeast), a common model organism used for studies of eukaryotic molecular biology. Under conditions of nitrogen limitation, S. cerevisiae activates a foraging program, which includes differentiation from the unicellular (yeast) form to a multicellular filamentous form that invades the growth substrate. We previously found that this process requires the Snf1 protein kinase, a member of the highly conserved Snf1/AMP-activated protein kinase (AMPK) family. The requirement of Snf1 for a nitrogen-regulated process was unexpected and interesting because Snf1 is best known for another function - regulating cellular responses to limitation for glucose, the preferred source of carbon and energy. Our current evidence provides further support for a novel role of Snf1 in signaling nitrogen limitation. We are using a combination of genetic and biochemical approaches to identify and characterize elements of this Snf1-dependent nitrogen-signaling pathway. The biomedical relevance of these studies is at least two-fold. First, filamentation is critical for virulence in fungal pathogens. Characterizing new molecular mechanisms of filamentous development in the S. cerevisiae model should broaden the spectrum of possible approaches to antifungal therapy. Second, the human counterpart of Snf1, AMPK, has been implicated in type 2 diabetes, obesity, cardiac disorders, and tumorigenesis. By studying novel regulatory roles of Snf1 in yeast, we expect to obtain further insights into AMPK function and its connection to human disease.
Barrett L., Orlova M., Maziarz M., Kuchin S. (2012) Protein kinase A contributes to the negative control of Snf1 protein kinase in Saccharomyces cerevisiae. Eukaryot. Cell 11, 119-128.
Kuchin S. (2011) Covering all the bases in genetics: simple shorthands and diagrams for teaching base pairing to biology undergraduates. J. Microbiol. Biol. Education 12, 64-66.
Orlova M., Ozcetin H., Barrett L., Kuchin S. (2010) Roles of the Snf1-activating kinases during nitrogen limitation and pseudohyphal differentiation in Saccharomyces cerevisiae. Eukaryot. Cell 9, 208-214.
Orlova M., Barrett L., Kuchin S. (2008) Detection of endogenous Snf1 and its activation state: application to Saccharomyces and Candida species. Yeast 25, 745-754.
Orlova M., Kanter E., Krakovich D., Kuchin S. (2006) Nitrogen availability and TOR regulate the Snf1 protein kinase in Saccharomyces cerevisiae. Eukaryot. Cell 5, 1831-1837.
Kuchin S., Carlson M. (2003) Analysis of transcriptional repression by Mig1 in Saccharomyces cerevisiae using a reporter assay. Methods Enzymol. 371, 604-616.
Kuchin S., Vyas V.K., Kanter E., Hong S.-P., Carlson M. (2003) Std1p (Msn3p) positively regulates the Snf1 kinase in Saccharomyces cerevisiae. Genetics 163, 507-514.
Vyas V.K., Kuchin S., Berkey C., Carlson M. (2003) Snf1 kinases with different beta-subunit isoforms play distinct roles in regulating haploid invasive growth. Mol. Cell. Biol. 23, 1341-1348.
Kuchin S., Vyas V.K., Carlson M. (2003) Role of the yeast Snf1 protein kinase in invasive growth. Biochem. Soc. Trans. 31, 175-177.
Kuchin S., Vyas V.K., Carlson M. (2002) Snf1 protein kinase and the repressors Nrg1 and Nrg2 regulate FLO11 expression, haploid invasive growth, and diploid pseudohyphal differentiation. Mol. Cell. Biol. 22, 3994-4000.
Vincent O., Kuchin S., Hong S.P., Townley R., Vyas V.K., Carlson M. (2001) Interaction of the Srb10 kinase with Sip4, a transcriptional activator of gluconeogenic genes in Saccharomyces cerevisiae. Mol. Cell. Biol. 21, 5790-5796.
Vyas V.K., Kuchin S., Carlson M. (2001) Interaction of the repressors Nrg1 and Nrg2 with the Snf1 kinase in Saccharomyces cerevisiae. Genetics 158, 563-572.
Vincent O., Townley R., Kuchin S., Carlson M. (2001) Subcellular localization of the Snf1 kinase is regulated by specific beta-subunits and a novel glucose signaling mechanism. Genes Dev. 15, 1104-1114.
Kuchin S., Treich I., Carlson M. (2000) A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. Proc. Natl. Acad. Sci. USA 97, 7916-7920.
Treitel M.A., Kuchin S., Carlson M. (1998) Snf1 protein kinase regulates phosphorylation of the Mig1 repressor in Saccharomyces cerevisiae. Mol. Cell. Biol. 18, 6273-6280.
Kuchin S., Carlson M. (1998) Functional relationships of the Srb10-Srb11 kinase, CTD kinase I and the transcriptional corepressor Ssn6-Tup1. Mol. Cell. Biol. 18, 1163-1171.
Song W., Treich I., Qian N., Kuchin S., Carlson M. (1996) SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Mol. Cell. Biol. 16, 115-120.
Kartasheva N.N., Kuchin S.V., Benevolensky S.V. (1996) Genetic aspects of carbon catabolite repression of the STA2 glucoamylase gene in Saccharomyces cerevisiae. Yeast 12, 1297-1300.
Kuchin S., Yeghiayan P., Carlson M. (1995) Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. Proc. Natl. Acad. Sci. USA 92, 4006-4010.
Kuchin S.V., Kartasheva N.N., Benevolensky S.V. (1993) Genes required for the derepression of an extracellular glucoamylase gene, STA2, in the yeast Saccharomyces. Yeast 9, 533-541.
Suntsov N.I., Kuchin S.V., Neystat M.A., Mashko S.V., Benevolensky S.V. (1991) Production of the STA2-encoded glucoamylase in Saccharomyces cerevisiae is subject to feed-back control. Yeast 7, 119-125.
Kuchin S.V., Neystat M.A., Gerasimenko O.G., Mashko S.V., Benevolensky S.V. (1990) Mutational analysis of the starch utilization system of Saccharomyces cerevisiae. Mol. Biol. Mikrobiol. Virusol. 5, 27-29.