Comparative Genomics and Pathogenesis of Tuberculosis

结核病的比较基因组学和发病机制

• 批准号: 7340510
• 负责人: SUSAN P HOLMES
• 金额: $ 6.68万
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7340510
• 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(申请人提供)：结核病是一个主要的全球健康问题。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。到目前为止，印度次大陆报告的谱系与世界上大多数研究实验室使用的参考菌株H37Rv和Erdmann具有不同的基因组特性。随着新的诊断测试、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发生在印度的结核分枝杆菌谱系的基因组特性、发病机制和宿主与病原体的相互作用，这些疾病在世界上造成了很大的负担。 我们推测，发生在印度南部的结核分枝杆菌流行谱系与其他谱系具有不同的致病特征。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、基因分型的克隆来验证这一假设。具体地说，我们将1)使用IS6110 RFLP、SPOGLING、基因组缺失和系统发育分析来鉴定印度南部结核病基于人群的分子流行病学研究中的结核分枝杆菌分离株；以及2)鉴定人类宿主人口中的结核分枝杆菌克隆，以确定克隆特异性疾病发生率。 该研究计划是印度金奈结核病研究中心(TRC)和加利福尼亚州斯坦福大学之间的合作试点研究项目。我们期望这一试点项目：1)实现上述具体目标；2)促进参与的科学家与各自机构之间的研究、培训和技术转让；3)为国家卫生研究院未来的五年期拨款提案提供初步数据，以推进印度次大陆的研究战略。到这笔赠款结束时，我们将有工具来调查和鉴定印度洋-大洋洲地区的主要结核分枝杆菌克隆，并在其他体外实验系统中进一步表征这些主要克隆的致病机制。