Modeling the Flagella Regulon in Salmonella

模拟沙门氏菌的鞭毛调节子

• 批准号: 7140313
• 负责人: John E. Mittler
• 金额: $ 18.43万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140313
• 关键词: Salmonella typhimurium; bacterial proteins; cell cycle proteins; developmental genetics; flagellum; fusion gene; gene expression; genetic regulatory element; genetic transcription; mathematical model; microarray technology; model design /development; polymerase chain reaction; protein biosynthesis; transcription factor; western blottings

DESCRIPTION (provided by applicant): This is a collaborative project between a bacterial geneticist, a mathematical biologist and a mathematician that will use mathematical models to study the genetic networks responsible for the ordered assembly of the flagellum. To quantify the regulatory molecules responsible for the construction of the flagella, we will develop a system of differential equations to explain the kinetics of appearance of structural and regulatory proteins following induction of flagella regulon in S. typhimurium. The initial model will consist of a equations for approximately 18 key proteins and operons that govern the ordered assembly of bacterial flagella. We will then use quantitative Western-blot analysis, operon and gene fusions, micro-arrays, microscopy, and bacterial motility assays to estimate parameter values, test the assumptions of the model, and investigate other genes not incorporated in the initial model for flagella biosynthesis. This data will be used to create refined models that can be used to study the role of genetic feedbacks and time-delays in creating cyclic patterns. These refined models can also be manipulated to predict what would happen had these operons evolved differentially. For example, we could test theoretically what one would expect if some of some of the class 3 genes were under the control of a class 2 promoter. These theoretical predictions will then be tested in the laboratory using genetically manipulated strains. Because TTSS is a potential target for antibodies, a quantitative study of these regulatory molecules could aid in the development of such vaccines. This is an easy-to-manipulate system in which structures can be easily visualized. Thus, we propose that the flagella could serve a model system for complex regulatory systems.

描述（由申请人提供）：这是细菌遗传学家，数学生物学家和数学家之间的协作项目，该项目将使用数学模型来研究负责鞭毛有序组装的遗传网络。为了量化负责鞭毛构建的调节分子，我们将开发一个微分方程的系统，以解释在Typhimurium S. typhimurium诱导鞭毛调节后结构和调节蛋白的外观。初始模型将由约18个关键蛋白和操纵子的方程组成，该方程控制细菌鞭毛的有序组装。然后，我们将使用定量的西部印迹分析，操纵子和基因融合，微阵列，显微镜和细菌运动测定法来估计参数值，测试模型的假设，并研究未纳入鞭毛生物合成的初始模型中的其他基因。这些数据将用于创建精致的模型，该模型可用于研究遗传反馈和时间延期在创建环状模式中的作用。这些精制模型也可以操纵，以预测这些操纵子的进化会发生什么。例如，我们可以从理论上测试如果三级基因中的某些基因中的某些人在2类启动子的控制下会期望。然后，将使用遗传操纵菌株在实验室中测试这些理论预测。由于TTSS是抗体的潜在靶标，因此对这些调节分子的定量研究可以帮助开发此类疫苗。这是一个易于操纵的系统，可以轻松地将结构可视化。因此，我们建议鞭毛可以为复杂的调节系统提供模型系统。