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Welcome to the Gasch Lab Elucidating stress-activated signaling networks

The Role, Regulation, & Evolution of Yeast Stress Responses

Our lab combines functional and comparative genomics, computational biology, and traditional techniques in genetics, biochemistry, and molecular biology to understand the role, regulation, and evolution of eukaryotic stress responses. All organisms must be able to sense and respond to their environment and defend themselves against environmental stress.

Through extensive transcriptome profiling in budding yeast, we previously identified a large gene expression program, called the environmental stress response (ESR), that is activated by many types of stress. The ESR consists of ~1000 gene expression changes and includes ~600 repressed genes and ~350induced genes.  The program is coordinated with specialized gene expression changes that provide specialized defense against particular conditions.  Activation of the ESR is not required to survive the initial stressor, but rather serves a critical role in surviving subsequent stresses through acquired stress resistance

The ESR is triggered by diverse types of stress, however the regulation of this program is condition-specific and governed by many different transcription factors, RNA binding proteins, and upstream signaling pathways depending on the conditions. We are taking an integrated approach to elucidate the signal transduction network that governs this response. In addition to learning how the ESR is coordinated, we are using this system to decipher rules of signal transduction and transcriptional regulation in this model eukaryote.We are also exploring the evolution of gene expression regulation, signal transduction, and environmental interactions. Using comparative genomic approaches, our work is revealing the variation in stress-triggered gene expression changes within and between species in the Ascomycete clade. This information, coupled with genomic comparisons of the more than 20 fungal genomes currently available, is being used to develop models for the evolution of gene expression patterns and environmental responses.

In addition to studying how evolution works, we also exploit evolution in our biofuels research.  As part of the Great Lakes Bioenergy Research Center (GLBRC), we aim
to engineer yeast strains to produce economical biofuels from available plant biomass, including plant cellulosic material.

There are two key bottlenecks to microbial fermentation of cellulosic biomass:
  • Chemical processing required to release sugars generates many byproducts that are stressful for yeast, limiting their ability to produce biofuels;
  • Saccharomyces cerevisiae, the current workhorse of bioethanol production, cannot utilize five-carbon ‘pentose’ sugars common in cellulosic material.  Our strategy is to study how wild yeast and fungi survive stress and consume pentose sugars, in order to engineer S. cerevisiae for industrial biofuel production from cellulosic material.