Molecular Genetics of Biofilm Formation

描述（由申请人提供）：细菌生物膜几乎可以在任何表面形成。由于生物膜对各种环境的影响，从医院病人的留置设备到水管，研究生物膜形成和维持的分子机制一直很有兴趣。因此，我们现在对许多模式细菌形成的生物膜的分子生物学有了大量的了解。虽然不同的细菌利用不同的途径来构建生物膜，但一个共同的特征出现了。细胞外基质——通常由多糖、蛋白质和核酸组成——将生物膜相关细胞固定在一起。如果我们要开发更好的方法来控制和操纵细菌生物膜，就需要充分了解控制基质生产的过程。在过去的二十年里，我们的实验室一直专注于研究革兰氏阳性模型细菌枯草芽孢杆菌形成生物膜的过程。因此，我们知道对这种生物体中控制基质产生的调节回路有了深刻的理解。我们的绝大多数研究都是在一组专门设计用于产生非常坚固的生物膜的实验室条件下使用小变化进行的。我们现在可以将生物膜分析提升到一个新的水平。以我们目前的理解为起点，我们现在将把我们的研究扩展到许多不同的环境条件。重要的是，我们将确定生物膜的形成如何受到其他细菌物种的影响，以及当它发生在植物根表面时它有何不同。我们拟对不同条件下枯草芽孢杆菌在生物膜形成过程中的不同反应进行系统级分析。这种方法以前还没有被用于研究生物膜。为了解决这一知识缺口，我们将重点研究以下四个具体目标：1)枯草芽孢杆菌生物膜研究新方法的开发和应用2)了解生物膜生理变化的系统水平方法3)生物膜形成的种间调节4)环境在根定植和生物膜形成中的作用。

DESCRIPTION (provided by applicant): Bacterial biofilms are able to form on almost any surface. Because of the impact that biofilms have on diverse environments, from indwelling devices in hospital patients to water pipes, there has been a great interest in investigating the molecular mechanisms underlying biofilm formation and maintenance. As a consequence we now know a large amount regarding the molecular biology of the biofilms formed by numerous model bacteria. While different bacteria utilize different pathways to build a biofilm, a common feature emerges. An extracellular matrix - generally composed of polysaccharides, proteins, and nucleic acids - holds the biofilm-associated cells together. A full understanding of the processes that control matrix production is required if we are to develop better ways to control and manipulate bacterial biofilms. Over the past two decades our laboratory has focused on studying the process of biofilm formation by the Gram-positive model bacterium Bacillus subtilis. As a result we know possess a deep understanding of the regulatory circuitry that governs matrix production in this organism. The vast majority of our studies have been carried out using small variations on one set of laboratory conditions that were specifically designed to yield very robust biofilms. We are now in a position to take biofilm analyses to the next level. With our current understanding as a starting point, we will now expand our studies to many different environmental conditions. Importantly, we will determine how biofilm formation is influenced by other bacterial species and how it differs when it happen on the surface of a plant's roots. We propose to carry out systems-level analyses of the different responses that B. subtilis mounts during biofilm formation under such diverse condition. Such an approach has not been taken to study biofilms before. To address this gap in knowledge, we will focus our work along the follow four specific aims: 1) Development and Application of New Methodologies to Study B. subtilis Biofilms. 2) A Systems-Level Approach to Understanding Changes in Biofilm Physiology. 3) Interspecies Modulation of Biofilm Formation. 4) The Role of the Environment in Root Colonization and Biofilm Formation.