Bacterial Biochemistry and Engineering
Our laboratory studies microbial biochemistry with an emphasis on understanding the molecular mechanisms that give rise to phenotypes in bacteria. Although our current understanding of the complexity of a bacterium is still emerging, it is becoming clear that the genetic and biochemical mechanisms that govern cellular homeostasis are far more sophisticated than we had imagined. Our approach to the study of bacteria is driven by the development of new capabilities for studying single cells or small groups of cells and the application of these techniques to dissect the molecular choreography within the cell. This research is interdisciplinary and is based on a fusion of techniques from biology, physics, engineering, and chemistry. The top-level goal of our research is to understand how the behavior and physiology of bacteria is encoded at the molecular level. The results of these projects drive the application phase of our research, which is aimed at using bacterial cells to produce new materials. We summarize several areas we are working on below.
Mechanisms that bacteria use to control the spatial and temporal organization of biomolecules in cells
The cartoon on the far left depicts biomolecular organization in a section of a bacterial cell (image courtesy of David S. Goodsell, SRI); the images on the bottom illustrate one area we study, in which cell wall curvature and strain on the membrane influences lipid and protein organization. We are actively building a connection between this area of bacterial cell biology and mitochondrial biochemistry.
Global assembly of the bacterial cell wall
We are identifying proteins that play a role in controlling the mechanical properties of the cell wall, with an emphasis on peptidoglycan assembly, remodeling, and regulation. As a well established target for antibiotics, this research develops an understanding of the biochemistry of cell wall biogenesis and characterizes new targets for antimicrobial agents.
Bacterial adaptation and fitness in fluctuating environments
We are particularly interested in community-wide behavior in bacterial swarms (graphic on right) and biofilms (graphic on far right) and their 'complex' behavior. Uncovering mechanisms that regulate this behavior has applications to a range of areas, including: human health, industry, and food security.
To study questions in bacterial cell biology, we develop and apply small molecules to gain insight into physiological mechanisms. As many of the proteins and processes we study are essential to bacteria, some of the small molecule inhibitors are promising leads for antibiotic development. The cartoon on the left depicts three classes of inhibitors we are actively developing.
To connect fundamental research to real-world problems, we look for opportunities to apply our research and solve unmet capabilities. This mindset has led us in several directions centered upon clinical microbiology, including point-of-need detection of pathogens in resource-poor settings (device at left).