Modern medicine has been revolutionized by the development of drugs with protein specificity. Our lab investigates the unanticipated consequences of these compounds on membrane structures. We are characterizing how amphiphilic drugs interact with cellular membranes to determine their impacts on membrane structure and protein function in human and microbial cells. To delve deeper into mechanistic details of drug permeation we use artificial lipid bilayer systems to study changes in dynamics and structure of the bilayer. This work will provide a foundation to build computational models of drug-membrane interactions that can inform on drug design and the unintended consequences of drugs.
Yeast as a Model for Human Diseases
The budding yeast, Saccharomyces cerevisiae, shares a surprising amount of genetic similarity with humans, making it a valuable model for understanding basic cellular processes. Utilizing yeast models, our lab studies the activities of RNA viral polyproteins, aiming to uncover how processing of polyprotein is informed by their structure and drive formation of replication organelles. A second area takes advantage of yeast to study oncogenic KRAS mutants providing a genetic system to study structure-function relationships.
We are developing models of natural flora using the worm gut and with home-built microfluidic devices to dissect the potential inter- and intra- communication between bacterial and fungal species. This is part of our efforts to detail the drug-gut-host axis and in wound infections that are comprised of mixed species.
Chromosome segregation, the process by which genetic material is accurately divided during cell division, is a fundamental aspect of cellular biology. Errors in this process can lead to diseases such as cancer. Using yeast as a model, our lab is interested in mechanisms that fine-tune chromosome segregation fidelity by post-translational modifications of the Dam1C, which forms the outer kinetcohore complex that directly binds to microtubules. We are particularly interested in how nutrient availability, such as glucose, can impact phosphorylation of Dam1C by the glucose sensing kinase PKA and the potential adaptive advantages that are afforded to yeast populations by modulating chromosome fidelity in response to changes in nutrient abundance/scarcity.