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；与趋化受体相关的灵活系链如何影响适应；以及信号蛋白是否在细胞质和膜之间移动以响应趋化刺激。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编写的新程序来解决这些和相关的问题。我们将通过与知名研究人员的合作，通过实验来测试和提炼我们的理论结果。我们的工作将促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对病原菌的侵袭和生物膜的形成起着关键作用。从更广泛的角度来看，我们的工作将有助于全面了解细菌和真核细胞中的信号转导途径。由于大肠菌群的趋化途径已经被很好地研究，我们有机会比其他类型的细胞更深入地探索它。因此，我们可以解决基本的问题，如途径的连续成分的综合相互作用，以及通过细胞质的扩散运动施加的限制。此外，计算和实验方法在我们的研究中的密切参与将有助于并受益于迅速扩大的系统生物学领域。

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.