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 evolution 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.
The Gasch Lab is dedicated to understanding the principles of eukaryotic environmental-stress defenses. 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.
Some key questions in the lab include:
* How do cells sense diverse environmental signals and then integrate those signals to identify the appropriate customized cellular response?
* How do inter-connected signaling networks in the cell transmit complex signals and coordinate a multi-faceted physiological response?
* How do cells set the balance between stress defense and growth, and how do defects in this decision point cause diseases such as cancer?
* How much do cellular responses vary across genetically identical cells, and is heterogeneity in the cellular response important for stress survival?
* How do responses vary across genetically unrelated individuals and what can this tell us about general principles of genotype-phenotype-environment interactions?
We use a variety of experimental tools, including bulk and single-cell transcriptomics, single-cell and single-molecule RNA and transcription factor analysis, comparative genomics and proteomics across strains and species. Many projects work at the interface of systems biology, comparative genetics, and evolutionary biology.