Smith Leif

Discovery of Novel Antimicrobial Agents My research focuses on the understanding of the structure and function of natural therapeutic products. This work will provide a foundation for research aimed at understanding their efficacy for use in the treatment and prevention of human and animal diseases and as potential biological control agents in agriculture. The discovery of novel antimicrobials and the study of antimicrobial function have significant relevance towards the development of therapeutics aimed at treating life-threatening diseases. Moreover, much of what we have learned about protein synthesis, DNA replication, enzyme function, and membrane physiology comes from the study of antimicrobials. The structural and functional characterization of new antimicrobial agents will provide new insights into cellular processes and membrane physiology, as well as provide means to rationally design new analogs that target microbial function. The discovery of new enzymes involved in natural product synthesis also offers invaluable information for understanding the complexity of microorganisms and provide tools for synthetic chemistry applications. My strength in this area of research lies in my cross disciplinary background, which encompasses antimicrobial development when I worked for Oragenics Inc. As a postdoctoral fellow at Oragenics Inc, I gained considerable amount of experience under the guidance of the distinguished Microbiology professor Dr. Jeffrey D. Hillman. It was here that I expanded my knowledge of Microbiology and learned several new biotechnology techniques involving preclinical testing of novel antimicrobials, which complemented my biophysical and molecular biology training at the University of Florida’s College of Medicine under the guidance of Dr. Arthur Edison. Our group laid the ground work for studies on the antibiotics mutacin 1140 and occidiofungin, i.e. production, purification and the structural determination, mechanism of action, and the assessment of their therapeutic potential. These studies are extremely important, given the rise in antibiotic resistance of Gram-positive pathogens and the need for new antifungal targets for treating serious fungal infection. Research Interests Novel peptide based antimicrobials are of great interest to my group. Whether ribosomally or non-ribosomally synthesized, these compounds often contain complex structures and systems leading to their production. The discovery of unique antibiotic structures and ascertaining their role in antimicrobial function are a fascinating area of research. Additionally, gaining an understanding of the function of the enzymes leading to their production is equally as interesting, because these enzymes may have utility in enzymatically synthesizing and engineering unique compounds. My strength in this area of research lies in my cross disciplinary background, which encompasses bacterial cultivation, bacterial genetics, fermentation and process biochemistry, structural determination using biophysical applications such as NMR and Mass Spectrometry, and experience in chemical modification and synthesis of natural products.