Specialties: Bacterial Genetics and Physiology, Molecular Microbiology: how are subcellular components synthesized and assembled at the appropriate time and place in response to internal cues and environmental conditions?

Despite their small size, bacterial cells have well-defined temporal and spatial architecture: various protein components localize to specific subcellular sites to execute precise functions during appropriate developmental stages of the bacterial life cycle. The key question is how information encoded in the genomic blueprint is articulated into a complex, three-dimensional structure that changes over time. Multiple regulatory mechanisms—including transcriptional control, signal transduction, proteolysis, and protein-protein interactions—cooperatively implement the genetic program. Caulobacter crescentus has emerged as a prominent model for elucidating the coordination of these regulatory mechanisms. Insights obtained through studies of C. crescentus are being exploited to gain a deeper understanding of how conserved components can behave differently across species. In particular, we are examining conserved proteins in Sinorhizobium meliloti, which is a symbiont that fixes nitrogen for specific legumes. Such investigation will help reveal how genetic divergence leads to distinct physiologies, adapted for different ecological niches.

There are currently three research projects in the lab:

1) Lactose metabolism. We have determined that a dehydrogenase is required for lactose metabolism in C. crescentus, suggesting an atypical degradation pathway, similar to that previously proposed for Agrobacterium tumefaciens. Genetic approaches and physiological and biochemical assays are being used to elucidate other components of the degradation pathway.

2) Twin-arginine transport. As opposed to the general secretory (Sec) pathway, which translocates unfolded proteins across the cell membrane, the twin-arginine transport (TAT) pathway allows export of folded proteins out of the bacterial cytoplasm. We are examining the significance of the TAT pathway in C. crescentus, which encodes a relatively high proportion of TAT substrates. Systematic analysis of these putative substrates will yield a better understanding of the basic rules that govern export by the TAT system, which is highly conserved across all domains of life.

3) Conserved, localized proteins. In C.crescentus, various regulatory proteins follow defined patterns of subcellular localization that contribute to asymmetric cell morphology: organelles specifically develop at one pole but not the other. These regulatory components are conserved in S. meliloti, a related bacterium that induces nodule formation in plant roots during symbiosis. However, S. meliloti cells are morphologically symmetric compared to C. crescentus. We are examining how these conserved components function in S. meliloti to regulate the assembly of surface organelles and how this regulation affects host-microbe interaction.