Research Abstract:
Most variation in the human population, including the susceptibility to diseases, is quantitative and genetically complex. Despite the primary importance of quantitative variation in medicine, the genetic basis of quantitative traits is poorly understood at the molecular level. Using yeast as a model system we are unraveling the molecular basis of naturally occurring phenotypic variation. We have assembled a collection of natural isolates of S. cerevisiae that show many phenotypic differences. Using a combination of modern functional genomics and classical quantitative genetics we intend to quantify the relative contribution of coding versus non-coding polymorphism to this natural variation. We are also investigating the role that variation in gene expression plays in generating this phenotypic diversity.
A second focus of the lab is to gain the ability to predict the expression pattern of a gene based on the sequence of its promoter. To this end we are developing new technologies to assay large numbers of engineered promoters with different combinations of cis-regulatory sites. Simultaneously we are developing a quantitative framework to use this data to predict the expression patterns both of promoters in the genome and of novel, engineered promoters.
Selected Publications:
Gertz J and Cohen BA. Environment-Specific Combinatorial cis-Regulation in Synthetic Promoters. Mol. Sys. Biol. 2009 5: 244.
Gerke JP, Lorenz K and Cohen BA. Genetic interactions between transcription factors cause natural variation in yeast. Science 2009 323: 498-501.
White MA, Riles L and Cohen BA. A systematic screen for transcriptional regulators of the yeast cell cycle. Genetics. 2009 181: 435-446.
Gertz J, Siggia E and Cohen BA. Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 2009 457: 215-218.
Witten JT, Chen CTL and Cohen BA. Complex genetic changes in strains of Saccharomyces cerevisiae derived by selection in the laboratory. Genetics 2007 177: 449-456.
Last Updated: 08/27/2009 |