Nutrients, cell growth, cell size, and cell cycle progression

Nutrient availability is a primary determinant of cell size. Single celled organisms cultured in nutrient rich medium can be up to three times the size of their counterparts cultured under nutrient poor conditions. Understanding the regulatory circuits and molecular mechanisms responsible for coordinating cell growth and cell size with nutrient availability and cell cycle progression is a primary objective of the lab.


Environmental determinants of antibiotic resistance & tolerance

Bacteria are exquisitely sensitive to their environment, displaying chameleon-like changes in growth rate and composition as they adapt to changes in nutrient availability, osmotic stress, and pH. Growth in nutrient poor conditions leads to accumulation of the small molecule, guanosine tetraphosphate or ppGpp. A global inhibitor of biosynthesis, ppGpp is implicated in antibiotic tolerance and the development of persister cells that survive for long periods in the presence of bacteriocidal compounds. Taking advantage of our finding that drugs that inhibit fatty acid synthesis drive entry into a persister-like state, we are systematically identifying ppGpp-dependent mechanisms underlying tolerance to antibiotics targeting DNA replication, cell wall synthesis, and protein synthesis.   We are also investigating a newly identified link between environmental pH and resistance to cell wall active drugs.


Spatial and Temporal Control of Cell Division

In bacteria, cell division is initiated by assembly of the tubulin-like cytoskeletal protein FtsZ into a ring-like structure at the future division site. The FtsZ ring serves as a scaffold for assembly of the division machinery, and constricts at the leading edge of the invaginating septum during cytokinesis. Precisely orchestrated changes in FtsZ assembly dynamics ensure that bacterial cells divide in the right place and at the right time. However, the signals triggering FtsZ assembly at the onset of the cell cycle and driving FtsZ ring constriction at the end of the cell cycle remain elusive.  Identifying the regulatory factors coupling FtsZ assembly and division to cell growth and the cell cycle is a major focus of our research.

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