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 Barak A. Cohen,PhD Assistant Professor
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The ultimate goal of genetics, and therefore of genomics, is to understand the relationship between genotype (sequence) and phenotype (function). Our primary aim is to gain the ability to predict (and mathematically model) the phenotypic outcome of mutations (polymorphisms). Achieving this aim will depend critically on our ability to understand the interactions among the nucleic acids, proteins, and other metabolites that comprise genetic regulatory networks. To this end we are applying both experimental and computational approaches to unravel the rules that govern the interactions among sets of genes that contribute to the same phenotype. Currently we are focusing our efforts in four areas.
1) Complex Traits. Using yeast as a model system we are studying the genetic 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. 2) in vitro evolution. As a complement to our studies of natural variation we also evolve strains in the lab, through long term growth and selection, to show different phenotypes. By identifying the mutations that are responsible for the phenotypic changes that arise in these strains we hope to better understand the role of coding versus non-coing mutations in adaptive evolution. 3) Engineering Gene Expression. We aim 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. 4) Conserved Non-Coding DNA. Our interest in non-coding DNA has recently been amplified by studies demonstrating that there is more conserved non-coding DNA (3%) in the human genome than conserved coding DNA (1.5%). We are studying one class of conserved non-coding elements in the human genome, the so-called "ultra-conserved" elements that consist of long runs of perfect conservation in human-mouse-rat alignments. Surprisingly, although these sequences are perfectly conserved over tens of millions of years we find polymorphism in these elements within human populations. We are now studying the patterns of polymorphism in these elements to try and better understand the forces that maintain these sequences at such high levels of conservation |