Our laboratory is part of the Microbial Sciences Institute at the Yale West Campus. Our group studies the temporal and spatial mechanisms involved in bacterial cell replication, with emphasis on chromosome dynamics, cell division, cell cycle regulation, and cell morphogenesis.
Cellular life cannot be sustained and propagated without temporal and spatial organization. Even bacteria, once mistakenly perceived as tiny jumbles of molecules, rely on temporal and spatial organization for many essential processes. It is now well established that bacteria are polarized, possess a cytoskeleton, order their chromosomes in space, localize proteins, and depend critically on this surprisingly exquisite cellular organization. Despite the surge of information about bacterial cell biology in the last decade, our knowledge is still at an early stage and many fundamental questions remain to be solved, providing unique opportunities to make new and exciting discoveries in this emerging discipline.
Our laboratory addresses the molecular and physical mechanisms involved in the internal organization of bacteria at several levels, from its origin, maintenance and replication in time and space to its function in cellular physiology and morphogenesis. We also probe the governing rules by which bacterial cells integrate cell growth and cell cycle events. We use three primary model systems: Escherichia coli, Caulobacter crescentus and the Lyme disease agent Borrelia burgdorferi, each having distinct advantages. On one hand, there is a wealth of knowledge on E. coli and studies are facilitated by the availability of large collections of strains, tools and databases. On the other hand, the highly polarized dimorphic C. crescentus provides a unique set of strengths for addressing questions pertinent to positional and temporal information. Cellular asymmetry is morphologically apparent in C. crescentus by the presence of polar appendages (e.g., stalk, pili and flagellum), and by the obligatory asymmetric division that yields daughter cells of different size, fate and morphology. This bacterium also displays a complex morphology and it possesses all three major types of cytoskeletal elements, MreB (actin homolog), FtsZ (tubulin homolog) and crescentin (intermediate filament-like protein). With the human pathogen B. burgdorferi, we investigate how unusual properties in bacterial growth and replication may contribute to pathogenesis and disease.
All the processes we study depend on the physical and chemical properties of the cell. In recent years, we discovered that the bacterial cytoplasm does not behave as a simple viscous fluid. Instead, it exhibits non-linear dynamics. These dynamics arise due to the nature of the cytoplasm: it is a complex material, crowded by long entangled polymers, compact polymers, aggregates and solutes. By introducing and tracking multiple foreign probes of different sizes in the cytoplasm, we are able to uncouple the contributions from chromosomal DNA and cytoplasm to particle dynamics. We are investigating how the physical and chemical properties of the cytoplasm impact bacterial physiology.
For our studies, we use an arsenal of genetic, biochemical, computational and cell imaging tools. A large part of our current effort is to improve our knowledge of the inventory of components involved in cellular organization and to characterize the function and interplay of known components and processes. To this end, we also develop new computational capabilities spanning image analysis, statistical inference and machine learning, and mathematical modeling.