1. Research Projects in Progress
My research expertise is in the genetics, physiology, and biochemistry of the cell envelopes of bacterial respiratory pathogens, with a special focus on the cell wall peptidoglycan.
1. Biosynthesis of the mycobacterial cell wall. Our current research activities focus on understanding the genetics and biochemistry of cell envelope biosynthesis in Mycobacterium tuberculosis and related mycobacteria with the goal of identifying new targets that can be translated into the development of novel anti-tuberculosis drugs. Our studies focus on four aspects of the peptidoglycan of mycobacteria: 1) identifying the enzymes responsible for DAP-DAP cross links in the cell wall and their importance for cell survival under non-replicating conditions, 2) understanding the role of carbohydrate hydroxylation and amino acid amidation on peptidoglycan physiology, 3) understanding the function of unusual L,D-transpeptidase enzymes that may modify the cell wall, and 4) understanding the factors that contribute to antibiotic resistance in M. tuberculosis. These research activities include collaborations with Dr. Dean Crick and Dr. Sebabrata Mahapatra (Colorado State University, Fort Collins, CO).
2. We are also collaborating with Dr. Scott Butler in the Department of Microbiology and Immunology here at the UR to investigate the function of toxin-antitoxin genes in M. tuberculosis and their potential role in latency in tuberculosis.
Tularemia and Biodefense Research
1. Development of genetic tools for Francisella tularensis and investigations into tularemia pathogenesis. Our early work on Francisella was to develop genetic methods to manipulate Francisella tularensis, the causative agent of tularemia and a Category A Select Agent. This work focused on developing new plasmid vectors, selectable markers, a method of allelic exchange and transposon mutagenesis, single-copy chromosomal integration systems, and protein secretion reporter systems. Future plans include the development of projects to investigate Francisella cell wall physiology and the roles that cell envelope components have in the innate immune response and tularemia pathogenesis.