Eukaryotic Pathogenesis; Gene Expression; Infectious Disease; Microbial Pathogenesis; Microbiology; Molecular and Cellular Biology; Protein Function and Structure; RNA; Transcription and Translation
In my laboratory, we use molecular biological and biochemical approaches to study Trypanosoma brucei, the causative agent of African sleeping sickness, and Trypanosoma cruzi, which causes Chagas disease in South and Central America. Treatment for these diseases is severely limited due to increasing drug resistance and lack of available drugs. The goal of our work is to discover and exploit critical events that occur in the parasite life cycle that may be used to prevent growth or transmission of the parasite.
The major project in my laboratory examines the ribosome, the complex molecular machine that drives protein synthesis. While many features of the ribosome and its assembly pathway are conserved in the parasites we study, we have identified features that are very different from the human host. Our laboratory discovered a pair of trypanosome-specific RNA binding proteins, P34 and P37, that are part of a unique preribosomal complex that is essential for ribosomal biogenesis and survival of trypanosomes. This may suggest that the interaction of these proteins with other components of the ribosomal assembly pathway can be developed as targets for chemotherapy. We are developing a high-throughput screen for small molecules that disrupt the complex in trypanosomes and do not harm the human host. My team and I also collaborate with Dr. Joachim Frank at Columbia University on a project to examine the structure of the ribosome and intermediates in the pathway of assembly using cryo-electron microscopy (cryo-EM). These experiments will provide important information about the unique features of the structure and function of the trypanosome ribosome and further our discovery of potential drug targets.
In addition, we continue in a long-standing collaboration with Dr. Beatriz Garat at the Universidad de la Républica in Uruguay, examining both DNA and RNA binding proteins which regulate gene expression in Trypanosoma cruzi.
The balance of graduate, undergraduate and medical students and postdoctoral researchers I mentor changes from year to year, though the international quality I strive to maintain has distinguished my laboratory for years: I enjoy having students from around the world as part of my research team. I am the course director for, and lecture in Critical Analysis and Eukaryotic Pathogens. I am also the course director for Eukaryotic Gene Expression and the co-course director for Molecular Parasitology.