LIPOOLIGOSACCHARIDE BIOSYNTHESIS IN NEISSERIACEAE

描述（改编自申请人摘要）：淋病奈瑟菌是 美国每年有超过一百万的淋病病例 与治疗淋病相关的总医疗保健费用，以及 由该微生物引起的感染引起的并发症超过1 十亿美元。一种有效的疫苗将大大减少 相关的医疗保健费用。这项提案的重点是阐明遗传 负责表达生物体的一种主要 表面抗原，脂寡糖（LOS）。在将要描述的工作中，我 将通过基因克隆和基因互补技术， 是LOS生物合成所必需的。我会用DNA来描述这些基因 序列分析，确定基因产物的生化特性， 决定它们在生物合成过程中的作用。由于淋球菌的种类 它的服务水平，取决于主机和当地环境，研究 其合成的遗传调控是必要的。稳定的LOS产生菌株 让我们能够剖析LOS在疾病过程中的作用。我 将构建一系列基因定义的LOS突变体， LOS结构。这些菌株也将使我们能够研究 该分子与其他细胞表面成分的表达。 了解LOS的表达方式将使我们能够设计 测试每种细胞表面成分在疾病中的作用的实验 过程通过了解疾病和表达之间的关系 我们可以设计疫苗来预防 特定人群的疾病。

Description (adapted from the applicant's abstract): Neisseria gonorrhoeae is responsible for over 1 million cases of gonorrhea each year in the United States and the total health care costs associated with treating gonorrhea, and complications that arise from infections caused by this organism exceed 1 billion dollars per year. An effective vaccine would dramatically reduce the associated health care costs. This proposal focuses on elucidating the genetic mechanisms responsible for the expression of one of the organism's principal surface antigens, lipooligosaccharide (LOS). In the work to be described, I will identify by gene cloning and genetic complementation techniques, genes required for the LOS biosynthesis. I will characterize these genes by DNA sequence analysis, define the biochemical properties of the gene products and determine their role in the biosynthetic process. Since the gonococcus can vary its LOS, depending on the host and the local environment, studies on the genetic regulation of its synthesis are warranted. Stable LOS-producing strains are needed to allow us to dissect the role of LOS in the disease process. I will construct a series of genetically defined LOS mutants that express defined LOS structures. These strains will also allow us to study the interaction of the expression of this molecule with other cell surface components. Understanding how the expression of LOS is regulated will allow us to design experiments to test the role of each cell surface component in the disease process. By understanding the relationship between disease and the expression of a specific surface component, we can design vaccines that can prevent the disease in specific demographic groups.