During evolution, there has been a high level of conservation between the budding yeast Saccharomyces cerevisiae's cellular processes and those of mammalian cells. The Baetz laboratory is exploiting powerful systems biology tools and the model organism yeast as a discovery platform for two areas of research: first, identifying novel targets of the enzyme family lysine acetyltransferases that regulate cell cycle progression, chromosome stability, metabolism and stress response, and second, deciphering the biological impact of lipid dysregulation. Given the conservation between yeast and man, our research will be of direct relevance to human cancer biology, metabolic and neurodegenerative diseases.
The Baetz lab accepts students from graduate programs in Biochemistry.
Research Program
The Baetz laboratory exploits the cross-species conservation of biochemical pathway function between yeast and human cells to gain insights into disease mechanism and the mode of action of various compounds. We are developing and applying high throughput yeast chemical and functional genomic screening along with proteomics to two areas of research interest.
The first of these is the study of lysine acetyltransferase (KAT) enzymes. Acetylation of KAT enzymes regulates protein function in a number of ways, including altering the localization, activity, stability and physical interactions of the target protein. Traditionally, lysine acetylation was thought to be largely a nuclear event; however, recent systematic screens have established acetylation as a ubiquitous and
conserved post-translational modification occurring on thousands of proteins in the cell. We are particularly interested in the S. cerevisiae KAT NuA4: disruption of its KAT activity causes a myriad of phenotypes including defects in chromosome segregation, cytoskeleton rearrangements, metabolism and stress response. We are using both functional genomic and proteomic approaches to identify novel targets of NuA4 and other KATs. As the human equivalent of NuA4 is mis-regulated in a variety of cancers, identifying the proteins that NuA4 regulates allows us to recognize targets for drugs that may one day be used in treating disease.
Second, we are studying chemical genomic approaches to deciphering the biological impact of lipid dysregulation in neurodegenerative diseases, particularly the pathways mediating the cellular effects of a series of alkylacylglycerophosphocholine species that have been associated with Alzheimer ’s disease progression. By harnessing the versatility of Saccharomyces cerevisiae we can quickly unravel mechanistic insights into the cellular pathways mediating the neurotoxic effects of lipids. Our end goal is to identify proteins and pathways that could be targeted to buffer the effects of neurotoxic lipids and slow the progression of Alzheimer’s disease.