The ability of newly synthesized proteins to efficiently fold into their active 3-dimensional conformations is critical for cell viability. Failures in this process result in protein misfolding, which can result in proteins with altered functions, complete loss of function, or conformations prone to aggregation. Cystic fibrosis, cancer, and neurodegenerative diseases are just some examples of conditions in which altered protein folding and function have a negative impact on human life.
Molecular chaperones, also known as heat shock proteins, are a family of proteins tasked with the responsibility of ensuring proper protein folding and function in the cell. In addition, they assist cellular recovery from stress conditions, such as temperature or osmotic shock, in which proteins may become partially or completely denatured. Chaperones aid the refolding of affected proteins or facilitate the degradation of proteins that cannot be salvaged. Thus, molecular chaperones are essential components of cellular quality control systems that ensure proper protein folding, function, localization, prevent protein aggregation and, when appropriate, aid the degradation of misfolded proteins.
My laboratory uses the budding yeast Saccharomyces cerevisiae (also known as baker’s yeast or brewer’s yeast) as a eukaryotic model system to explore questions of cellular protein folding and degradation, with a particular focus on the roles of molecular chaperones in these processes. The two primary areas of research are 1) Uncovering the cellular requirements for and roles of the abundant and essential molecular chaperone, Hsp90 (see McClellan et al., 2007, Cell; Franzosa et al., 2011, PLoS One) and 2) Exploring the cellular requirements for the degradation of model misfolded proteins to better understand how misfolded proteins are recognized and targeted for destruction (see McClellan, 2012, Encyclopedia of Life Sciences; McClellan et al., 2005, Cell; McClellan et al., 2005, NCB).