Comparative Genomics and Pathogenesis of Tuberculosis

结核病的比较基因组学和发病机制

• 批准号: 7100036
• 负责人: SUSAN P HOLMES
• 金额: $ 8.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100036
• 关键词: Address; Applications Grants; California; Characteristics; Clinic; Clinical; Clinical Data; Collection; Country; Data; Databases; Diagnosis; Diagnostic tests; Disease; Epidemiologic Studies; Future; Genetic Polymorphism; Genomics; Genotype; Grant; Health; Human; In Vitro; India; Institution; International; Laboratory Research; Methods; Molecular; Mycobacterium tuberculosis; Numbers; Oligonucleotide Microarrays; Pathogenesis; Patients; Phylogenetic Analysis; Pilot Projects; Population; Population Study; Property; Public Health; Publications; Pulmonary Tuberculosis; Rate; Reporting; Research; Research Personnel; Research Project Grants; Research Training; Restriction fragment length polymorphism; Scientist; Study Subject; Surveys; System; Technology Transfer; Testing; Trees; Tuberculosis; United States National Institutes of Health; Universities; base; burden of illness; clinical phenotype; comparative; design; novel diagnostics; novel vaccines; pathogen; time interval; tool; tuberculosis drugs

DESCRIPTION (provided by applicant): Tuberculosis is a major global health problem. One fourth of the world's tuberculosis cases occur in India, which reports 2 million new cases annually. Recent studies suggest there are a limited number of major phylogenetic lineages of Mycobacterium tuberculosis worldwide. The lineages reported from the Indian subcontinent to date have different genomic properties than the reference strains H37Rv and Erdmann, which are used by most research laboratories around the world. As new diagnostic tests, new anti-TB drugs and new vaccines against tuberculosis are developed, there are compelling reasons to understand and consider the genomic properties, pathogenesis and host-pathogen interactions of the lineages of M. tuberculosis that occur in India and are responsible for a large burden of disease in the world. We hypothesize that the prevalent lineage of M. tuberculosis that occurs in southern India has different pathogenetic characteristics than other lineages. We will test this hypothesis using well-characterized, genotyped clones from a study in the Tiruvallur district, Tamil Nadu state. Specifically, we will 1) characterize the isolates of M. tuberculosis from a population-based molecular epidemiologic study of tuberculosis in southern India using IS6110 RFLP, spoligotyping, genomic deletions and phylogenetic analyses; and 2) characterize the clones of M. tuberculosis in the human host population to identify clone-specific rates of disease. The research plan is a collaborative pilot research project between the Tuberculosis Research Centre (TRC) in Chennai, India and Stanford University, California. We expect this pilot project to 1) address the specific aims outlined above; 2) further the research, training, and technology transfer between the participating scientists and their respective institutions; and 3) generate preliminary data for a future, five- year grant proposal to the NIH that advances research strategies for the Indian subcontinent. By the end of this grant, we will have the tools to survey and identify the predominant clones of M. tuberculosis in the Indo- Oceanic region and to further characterize the pathogenesis of those predominant clones in other experimental in vitro systems.

描述（由申请人提供）：结核病是一个主要的全球性健康问题。世界上四分之一的结核病病例发生在印度，印度每年报告200万新病例。最近的研究表明，世界范围内结核分枝杆菌的主要系统发育谱系数量有限。迄今为止，印度次大陆报道的谱系与世界上大多数研究实验室使用的参考菌株H37 Rv和Erdmann具有不同的基因组特性。随着新的诊断试验、新的抗结核药物和新的抗结核疫苗的开发，有令人信服的理由来理解和考虑M.结核病发生在印度，是世界上一个巨大的疾病负担。 我们假设M.发生在印度南部的结核病具有与其他谱系不同的致病特征。我们将使用泰米尔纳德邦Tiruvallur区的一项研究中的特征良好的基因型克隆来验证这一假设。具体而言，我们将1）表征M的分离株。结核病从人口为基础的分子流行病学研究结核病在印度南部使用IS 6110 RFLP，spoligotyping，基因组缺失和系统发育分析;和2）表征M的克隆。结核病在人类宿主人群中的流行，以确定疾病的克隆特异性比率。 该研究计划是印度钦奈结核病研究中心和加州斯坦福大学之间的合作试点研究项目。我们希望这个试点项目1）解决上述具体目标; 2）进一步研究，培训和参与科学家及其各自机构之间的技术转让;和3）为未来提供初步数据，向NIH提供为期五年的赠款提案，以推进印度次大陆的研究战略。到本基金结束时，我们将拥有调查和鉴定M.结核病在印度洋地区，并进一步表征这些占主导地位的克隆在其他体外实验系统的发病机制。