Regulation of polar development in Caulobacter

描述（由申请人提供）：细菌细胞的内部组织对许多复杂过程至关重要。例如，细菌能够在恶劣条件下生存，或通过产孢和分泌毒力因子感染宿主细胞。产孢和在许多情况下毒力因子的分泌需要蛋白质的亚细胞定位。荧光标记的使用表明，蛋白质可以在细胞内具有动态定位模式，但亚细胞定位在调节调节蛋白活性中的作用仍不清楚。组氨酸激酶是一类主要的细菌调节蛋白，在响应内部和外部信号的信号通路中起作用。本研究利用新月形茎杆菌作为细胞分化调节的模型系统，试图确定组氨酸激酶及其假定的定位因子如何帮助调节由不对称分裂引起的一个后代的发育。本研究的目的是：1)确定调节发育的组氨酸激酶与已知的发育调节剂之间的关系，该调节剂是细胞内蛋白质极性定位的主要靶点。这将通过上位分析来确定它们是否在相同的调控途径中，这两种蛋白质是否相互作用并且是彼此极性定位所必需的，以及它们基因中的单突变或双突变如何影响全局基因表达来完成。2)确定两种蛋白在运动调节中的作用。这将通过确定组氨酸激酶的激酶活性的作用和定位因子对该活性的影响，以及通过鉴定和研究相同调控途径中的基因来完成。总之，这些实验将有助于了解亚细胞定位如何调节调节蛋白的活性。

DESCRIPTION (provided by applicant): The internal organization of bacterial cells is critical for many complex processes. For example, bacteria are able to survive harsh conditions or infect host cells through sporulation and secretion of virulence factors. Sporulation and in many cases virulence factor secretion require subcellular localization of proteins. The use of fluorescent tags has shown that proteins can have dynamic localization patterns within the cell, but the role of subcellular localization in the modulation of regulatory protein activity is still unclear. Histidine kinases are a major class of bacterial regulatory proteins that act in the signaling pathways responding to both internal and external signals. Using Caulobacter crescentus as a model system for the regulation of cell differentiation, this study seeks to determine how a histidine kinase and its putative localization factor help regulate the development of one of the offspring resulting from asymmetric division. The aims of this study are to: 1) Determine the relationship between a histidine kinase that modulates development and a known developmental regulator that is a major target for the polar localization of proteins within the cell. This will be accomplished by determining if they are in the same regulatory pathway through epistasis analysis, if these two proteins interact and are required for each other's polar localization, and how global gene expression is affected by single or double mutants in their genes. 2) Determine the role of the two proteins in the regulation of motility. This will be accomplished by determining the role of the kinase activity of the histidine kinase and the impact of the localization factor on this activity and by the identification and study of genes in the same regulatory pathway. Together these experiments will help understand how subcellular localization can modulate the activity of regulatory proteins.