In the post-genomic era, quantitative modeling is essential for understanding critical cell functions such as cell movement, cell signaling and cell division. Traditional models of cellular processes often rely on biochemical descriptions of enzymatic events, with no information regarding biomaterial properties or the role of mechanical forces in regulating biochemistry. However, mechanical forces often have a profound influence on biochemistry, and can lead to reorganizations of biological matter and open new biochemical pathways. Improved understanding of cellular force generation and regulation is a goal of this proposal. In particular, we focus on the bacterial systems and ask how forces are generated in the bacterial cytokinetic ring (Z-ring), and how forces influence the observed geometric shape of the bacterial cell. Quantitative models of cell wall growth are proposed. Connections between genetic components and the observed cell shape are investigated using a combination of modeling and experiments. In addition, we propose that the contraction of the Z-ring is driven by lateral interaction between FtsZ filaments. This mechanism does not rely on chemical energy derived from GTP hydrolysis. We propose to test this idea using single molecule and fluorescence imaging experiments. The results of this proposal will build foundations for understanding cell cycles in both prokaryotic and eukaryotic cells, and elucidate the role of mechanics in guiding cell morphogenesis, cell movement and biological functions in general. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page.
Disease-causing microbes that have become resistant to drug therapy are an increasing public health problem. The recent discovery of several bacterial cytoskeletal proteins with shape-defining function provides new molecular targets for anti-bacterial treatments. This proposal seeks to understand the molecular mechanisms behind the prokaryotic cell cycle, develop models to open new strategies to combat pathogens, and reveal principles for the engineering of beneficial microbes. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page
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