Research

In our laboratory, we take an interdisciplinary approach to study the fundamental mechanisms by which bacteria grow, divide, and adapt to different growth conditions. We use the dimorphic alphaproteobacterium Caulobacter crescentus as one model for these studies, as its curved-rod morphology and well-characterized cell and developmental cycle make it particularly well-suited to address questions of morphogenesis and growth control. We recently initiated studies into a second alphaproteobacterium - the obligate intracellular, tick-borne human pathogen Rickettsia parkeri - to investigate the cell biology of the enigmatic Rickettsiales. With their distinct lifestyles and physiology, Caulobacter and Rickettsia present complementary models to understand both conservation and evolution of growth and adaptation mechanisms among the Alphaproteobacteria.

We use a multi-pronged approach combining genetics, genomics, imaging, biochemistry, and in vitro reconstitution to understand the cell biology and adaptation mechanisms of these organisms. We are highly collaborative and love to work with specialists in advanced imaging techniques, new analytical approaches and tools, structural biology, and complementary bacterial species or hosts. Our fundamental research into essential aspects of bacterial physiology will inform antibiotic development and resistance mechanisms, as well as synthetic cell biology efforts.

Our current work in Caulobacter focuses on two primary questions: (1) how do bacteria carry out cell division and (2) what is the role of the cell envelope in sensing and adapting to environmental changes? In recent years, we have begun to map a pathway from the master regulator of division, FtsZ, to the cell wall synthases FtsWI. We are currently pursuing a mechanistic understanding of how this pathway coordinates chromosome segregation with cell wall synthesis. On the adaptation side, we have become intrigued by envelope components called osmoregulated periplasmic glucans (OPGs) that play poorly understood roles in morphogenesis, growth, and resistance to envelope stress and antibiotics. We are using biochemical and genetic approaches to better understand OPG metabolism and function.

To begin to study R. parkeri biology, we developed quantitative tools to measure morphology and growth as well as to visualize proteins within live bacterial cells. In addition, we have embarked on developing a library of transposon insertion mutants to facilitate genetic approaches to understanding rickettsial cell biology. We now have R. parkeri mutants in hundreds of unique genes for further study.

With these tools in hand, we are pursuing an understanding of fundamental aspects of R. parkeri biology. Some current projects are exploring the mechanisms and functions of cell polarity in R. parkeri, regulation of surface proteins that mediate host interactions, and signaling pathways the mediate hosting sensing and adaptation.

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