BACTERIAL CHEMOTAXIS: A COMPUTER-BASED STUDY

描述（由申请人提供）：在这个项目中，我们将使用新开发的计算方法来解决细菌趋化性中的突出问题。这些问题包括细菌如何在复杂的自然环境中导航;与趋化性受体相关的柔性系绳如何影响适应;以及信号蛋白是否在细胞质和细胞膜之间移动以响应趋化性刺激。我们建议通过我们小组已经制定的现有计算方法以及我们将为此目的编写的新颖程序来解决这些问题和相关问题。我们将通过与现有研究人员的合作，通过实验来测试和完善我们的理论结果。我们的工作将推进对这种细菌趋化性的理解，这种趋化性已被证明在临床和工业环境中致病菌的侵袭性和生物膜的形成中起着至关重要的作用。从更广泛的角度来看，我们的工作将有助于在细菌和真核细胞的信号转导途径的一般理解。由于大肠菌群的趋化途径研究得如此之好，我们有机会比其他细胞类型更深入地探测它。因此，我们可以解决的基本问题，如整合的相互作用的连续组件的途径，并通过细胞质的扩散运动所施加的限制。此外，在我们的研究中，计算和实验方法的密切参与将有助于系统生物学快速扩展的领域，并从中受益。

DESCRIPTION (provided by applicant): In this project, we will use newly developed computational methods to address outstanding issues in bacterial chemotaxis. These include the question of how bacteria navigate through complex natural environments; how the flexible tethers associated with the chemotaxis receptors influence adaptation; and whether signaling proteins move between the cytoplasm and the membrane in response to chemotactic stimulation. We propose to tackle these and related issues by existing computational methods already formulated by our group as well as novel programs that we will write for the purpose. We will test and refine our theoretical results experimentally through collaborations with established investigators. Our work will advance the understanding of this bacterial chemotaxis, which has been shown to play a crucial role in the invasiveness of pathogenic bacteria and the formation of biofilms in clinical and industrial settings. From a broader perspective, our work will contribute to the general understanding of signal transduction pathways in both bacterial and eucaryotic cells. Because the chemotaxis pathway of coliform bacteria is so well studied, we have an opportunity to probe it in greater depth than is possible in other cell types. We can therefore address fundamental issues such as the integrative interaction of contiguous components of the pathway, and the constraints imposed by diffusive movements through the cytoplasm. Moreover, the intimate involvement of computational and experimental approaches in our study will both contribute to, and derive benefit from, the raidly expanding area of systems biology.