Bacterial Cell Division and the Dynamics of the Z-ring

描述（由申请人提供）：在后基因组时代，定量建模对于理解细胞运动、细胞信号传导和细胞分裂等关键细胞功能至关重要。传统的细胞过程模型通常依赖于酶促事件的生化描述，没有关于生物材料特性或机械力在调节生物化学中的作用的信息。然而，机械力往往对生物化学有着深远的影响，可以导致生物物质的重组，开辟新的生物化学途径。提高对细胞力产生和调节的理解是本提案的一个目标。特别是，我们专注于细菌系统，并询问如何在细菌细胞动力学环（Z环）中产生力，以及力如何影响观察到的细菌细胞的几何形状。提出了细胞壁生长的定量模型。遗传成分和观察到的细胞形状之间的连接进行了研究，使用建模和实验相结合。此外，我们提出的Z-环的收缩是由FtsZ细丝之间的横向相互作用。这种机制不依赖于GTP水解产生的化学能。我们建议使用单分子和荧光成像实验来测试这一想法。该提案的结果将为理解原核和真核细胞的细胞周期奠定基础，并阐明力学在指导细胞形态发生，细胞运动和生物功能中的作用。PHS 398/2590（Rev. 06/09）第1页 公共卫生相关性：对药物治疗产生耐药性的致病微生物是一个日益严重的公共卫生问题。最近发现的几种细菌细胞骨架蛋白具有形状定义功能，为抗菌治疗提供了新的分子靶点。该提案旨在了解原核细胞周期背后的分子机制，开发模型以开辟对抗病原体的新策略，并揭示有益微生物的工程原理。PHS 398/2590（Rev. 06/09）第1页

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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