Research in the Walker laboratory falls into two major areas. One is primarily directed towards addressing the problem of antibiotic resistance. We investigate bacterial pathways that may be targets for new antibiotics. We carry out detailed mechanistic and structural studies of known antibiotic targets with the expectation that a better understanding of how they function will lead to the ability to design improved antibiotics. We study the mechanisms of action of natural product antibiotics in order to understand the strategies nature has employed to kill bacteria. We work on strategies to discover new antibiotics as well as methods to modify natural product antibiotics to improve their properties. Finally, we explore the mechanisms by which resistance can develop to selected antibiotics. In our studies we employ biophysical approaches to study protein structure, biochemistry to probe enzyme function, genetics to explore gene function in selected microorganisms and to manipulate natural product biosynthetic pathways, and high throughput screening to discover compounds that interfere with biosynthetic pathways or processes of interest. We also make use of synthetic organic chemistry to enable some of our projects. Microorganisms we manipulate in the laboratory include Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus.
The second major research area focuses on understanding human O-GlcNAc transferase (OGT), a glycosyltransferase that modulates signaling pathways linked to glucose metabolism. We are interested in the structure and function, and in developing strategies to probe its biological roles.
HIM Building, 10th floor Room 1013
4 Blackfan Circle
Boston, MA 02115