A major goal in biology is to read an organism’s genome sequence and predict how that organism will look, behave, adapt, and reproduce. Putting this into practice remains a major challenge, in large part because we simply lack a deep understanding of how a genome sequence is enacted to create organisms that are more than the sum of their parts.
The Gasch Lab is interested in understanding fundamental relationships between genes, genomes, and environments that elicit complex organismal phenotypes. We study this through several models outlined below.
The Role, Regulation, & Evolution of Eukaryotic Stress Responses: Organisms exist in dynamic relationship with their environments, sensing and responding to environmental fluctuations that can influence how cells and organisms function. Many conditions, such as environmental toxins and extreme condition shifts, pose stressful situations that can perturb physiology if left unattended. Thus, all cells have intricate systems for sensing their environments, detecting when there is a problem, and mounting a response to maintain a healthy system. Organism-environment interactions have shaped organismal form and function over evolutionary timeframes, but they also affect individuals during their lifespan. In fact, defects in responding appropriately to cellular stress are linked to many diseases, including cancer and aging.
We integrate novel approaches in functional and comparative genomics, computational analysis, systems biology, and genetics and molecular analysis to understand how cells sense and respond to stress. We primarily study the model eukaryote budding yeast, Saccharomyces cerevisiae, the darling of systems biology that allows us to address new questions in stress biology with implications for other organisms including humans.
Natural variation and genotype-phenotype relationships. Budding yeast is an outstanding model in which to elucidate principles of gene-environment-phenotype relationships. Our lab incorporates studies of diverse S. cerevisiae strains, including many isolated from nature, to understand how phenotypes including stress tolerance vary across individuals. Integrating functional genomics, population genetics, systems biology, and our deep understanding of environmental responses provides a unique glimpse into this problem, and the power of yeast genetics allows us to elucidate genetic mechanisms of variation. An important area of study is understanding how gene-gene and gene-genome interactions modify how genetic variants function in one individual versus another, especially in the context of environmental changes.
Exploiting functional network evolution to identify and predict the effects of causal genetic variants. Predicting organismal phenotypes from their genome sequences will require new methods in both understanding genomes and predicting how variation in those genomes underlies phenotypic differences. We are working with a team of computational biologists, statistical genomicists, and human geneticists at UW-Madison to develop new methods in predicting and understanding causal genetic variants in human patients with polygenetic diseases. A key contribution from our lab is to incorporate massive amounts of functional genomic data collected from model organisms into network inference of human genetic data, through creative methods couched in evolutionary biology. We are currently developing and applying these methods in collaboration with WI sequencing center PreventionGenetics and as part of the new NHGRI consortium “Impact of Genomic Variation on Function” (IGVF). Find out more about available positions!