Biology and Biomedical Sciences: Molecular Cell Biology
Date of Award
Doctor of Philosophy (PhD)
Chair and Committee
Petra Anne Levin
Cell size control is of universal importance to all organisms. Regulation of cell size ensures that cells are of the appropriate size for a given growth condition or developmental fate. Nutrient availability is a primary determinant of cell size in bacteria. Bacterial cells, including the Gram-positive Bacillus subtilis and the Gram-negative Escherichia coli increase size in a nutrient-dependent manner. Cells cultured in nutrient-rich medium can be up to twice the size of their counterparts cultured in nutrient-poor medium, suggesting that bacteria have ways of sensing nutrient availability and transmitting this information to the division machinery.
This dissertation first examines the growth rate and nutrient-dependent cell size control in the Gram-positive model bacterium B. subtilis, how bacterial cells sense nutrient availability and transmit this information to the division apparatus to result in the smoothly graded cell size response to the incremental and rapid changes in nutrient availability. My findings also suggest that B. subtilis uses a cell-intrinsic, autonomous model system for detecting the achievement of a particular size.
Next, the substrate-induced regulation of the nutrient-dependent division inhibitor UgtP is characterized. In addition to UDP-glucose, I examined the effects of the acceptor substrate diacylglycerol on UgtP's activity. Findings presented here point to a potential link between cell envelope biogenesis and division. To further dissect the role of UgtP in the growth rate and nutrient-dependent cell size control, a structure/function analysis of UgtP is also described in this dissertation. Studies on UgtP mutants provide new evidence to suggest how UgtP's activity is regulated by itself, its substrates, and FtsZ.
This work yields three fundamental conclusions: 1) UDP-glucose, which serves as a proxy for nutrient availability, fine-tunes the oligomerization potential of the division inhibitor UgtP, thus dictating the amount of assembly competent FtsZ and resulting in the smoothly graded cell size response to nutrient availability, 2) B. subtilis cells detect the achievement of a particular size using a cell-intrinsic system that relies on the balance between FtsZ assembly and disassembly, which is modulated by the intracellular levels of active UgtP, and 3) the growth rate and nutrient-dependent cell size control governed by UgtP is regulated by its donor substrate UDP-glucose and its acceptor substrate diacylglycerol.
Chien, Anchun, "A Molecular Rheostat Coupling Cell Size to Nutrient Availability in Bacteria" (2012). All Theses and Dissertations (ETDs). 947.
Permanent URL: http://dx.doi.org/10.7936/K76D5R07