Role of regulatory genes in the gastrointestinal pathogen, Clostridium difficile

当患者在医院接受抗生素治疗时，他们有时会出现慢性腹泻或结肠炎综合征，治疗起来非常困难和昂贵。该项目涉及对通常导致这些胃肠道疾病的细菌的分析。我们知道这种微生物存在于医院环境中，并产生导致这些疾病的强有力的蛋白质毒素，但我们对实际疾病过程知之甚少。在大多数导致疾病的细菌中，都有调控网络来控制导致疾病过程的基因的表达。在这个项目中，我们的目标是了解这些调控网络如何在这种特定的细菌中运作。最新的分子生物学技术将被用来在功能水平上研究几个特定的调控基因。由于这种细菌的整个DNA序列现在已经知道，我们还将使用一种更广泛的研究方法，利用这一知识来检查这种细菌中存在的所有潜在的调控网络。最后，我们将开发新的致病细菌遗传分析方法，以便我们能够更好地阐明特定基因在疾病过程中的作用。通过了解这种细菌是如何控制与人类肠道细胞相互作用的蛋白质的产生而导致疾病的，我们希望能够防止此类疾病的发生。因此，该项目的成功完成将对改进控制和治疗这些慢性腹泻和结肠炎综合征的方法作出重大贡献。

When patients are treated in hospital with antibiotics they sometimes develop chronic diarrhoea or colitis syndromes that are very difficult and expensive to treat. This project involves the analysis of the bacterium that generally causes these gastrointestinal diseases. We know that this microorganism is present in the hospital environment and that it produces potent protein toxins that are responsible for these diseases but we know little about the actual disease process. In most bacteria that cause disease there are regulatory networks that control the expression of the genes responsible for the disease process. In this project, we aim to develop an understanding of how these regulatory networks operate in this particular bacterium. The latest techniques of molecular biology will be used to investigate several specific regulatory genes at the functional level. Since the entire DNA sequence of this bacterium is now known we will also use a broader research approach that makes use of this knowledge to examine all of potential regulatory networks that exist in this bacterium. Finally, we will develop new methods for the genetic analysis of the causative bacterium so that we will be better able to elucidate the role of specific genes in the disease process. By understanding how this bacterium controls the production of the proteins that interact with human intestinal cells to cause disease we hope to be able to prevent such diseases from occurring. The successful completion of the project therefore will make a major contribution to the development of improved methods for the control and treatment of these chromic diarrhoea and colitis syndromes.