The research of my laboratory focuses on elucidating the molecular principles underlying life phenomena using protein engineering approaches. This is achieved by setting simple working hypotheses and testing these in systematic experiments. Some recent themes are described below. While the subjects of research may appear to be quite different, they have a common theme of the structure-function relationship of proteins.

Evolutionarily “older” enzymes exhibit conserved function over long evolutionary processes. We are able to exploit the sophisticated features of such enzymes for purposes that are completely different to their biological function. For example, dUTPase is a homo-trimeric enzyme, which has a key role in the DNA synthesis pathway of many species. However, this enzyme is hijacked by some viruses, who use the trimeric structure for capsid formation rather than for its catalytic activity. My laboratory has been investigating this enzyme previously, and so future endeavors will focus on different developments.

Allosteric regulation is the phenomenon in which a protein with a certain function is regulated by an effector molecule, which binds to a site that is topographically different to its active site. Allosteric regulators typically cause structural changes in the target protein; thus, altering its function. γ-Aminobutyric acid (GABA) receptors are present on the surface of inhibitory synapses and inhibit excited neurons. These receptors are allosterically regulated by various molecules. We hypothesized that subsites along the cleft of the simpler insect GABA-type-B receptor could provide insight into the movement involved in allosteric regulation. The first phase of this study has been completed and detailed analysis is ready for development into in vitro, in vivo, and in-population studies. I look forward to participating in your research.

In the summer of 2022, we conducted an electrophysiological study of GABA receptor activity with Hope and Aaron in the lab, and discovered an unknown precipitate which formed in a solution of many constituents. We reaffirmed Le Chatelier’s principle to eliminate the cause of this precipitation. Based on this experience, I hypothesized that slight changes in experimental parameters such as concentration, pressure, and temperature would provide data to enable us to reproduce these environmental changes in the laboratory. Such experimental systems can be set up to represent aquatic animals and intestinal bacteria, and participation from undergraduate students is especially welcome.