Current Research and Scholarly Interests
Survival in changing environments requires the acquisition of new heritable traits. However, mechanisms that safeguard the fidelity of DNA replication often limit the source of such novelty to relatively modest changes in the genetic code. Thus, the acquisition of new forms and functions is thought to be driven by rare variants that occur at random, and are enriched during times of stress. We have begun to study an intriguing alternative hypothesis: that intrinsic links between protein folding and virtually every biological trait provide multiple avenues through which environmental stress can directly elicit heritable variation that drives evolution, disease, and development.
Our aim is to identify and characterize these mechanisms at the molecular level, integrating our findings to gain insight into the interplay among genetic variation, phenotypic diversity, and environmental fluctuations in complex cellular systems. Much of our work centers on the specific influence of molecular chaperones, proteins that help other proteins fold. Other projects focus on the induction of epigenetic variation that can be passed from one generation to another via self-perpetuating changes in protein conformation. Our work employs multidisciplinary approaches including biochemistry, genome-scale analyses, high-throughput screening methodologies, live cell imaging, microfluidics, and quantitative genetic techniques. Ultimately we seek to not only to understand mechanisms that link environmental stress to the acquisition of biological novelty, but also to identify means of manipulating them for therapeutic benefit and harnessing their power to engineer synthetic signaling networks.