M tuberculosis evasion of the innate immune response

描述（由申请人提供）：本提案描述了一个为期五年，由两部分组成的 结核分枝杆菌研究的职业发展计划。 该计划将在巴里布鲁姆博士的实验室进行， Eric Rubin博士的额外指导，无论是在免疫学部门， 哈佛公共卫生学院的传染病。候选人是 受过传染病方面的培训，并有建立一个 独立实验室研究M.结核病的发病机制， 重点研究分枝杆菌与宿主免疫反应和疫苗的相互作用 发展该计划的教学部分涉及以下课程： 在哈佛大学学习分子生物学和免疫学研究 该计划的一部分涉及探索两个假定的机制， 免疫逃避M.抑制IFN-γ信号传导， 抑制感染的巨噬细胞中诱导型IL-12的产生。具体 研究的目的是：1）确定Toll类 受体2（TLR-2）活化抑制IFN-γ信号传导或诱导性IL-12 生产; 2）鉴定M.结核病抑制所需基因 IFN-γ和IL-12信号转导的研究 分枝结核病;和3）表征这些中鉴定的基因 卡位

DESCRIPTION (provided by applicant): This proposal describes a five year, twopart career development program in the study of Mycobacterium tuberculosis. This program will be carried out in the laboratory of Dr. Barry Bloom with the additional guidance of Dr. Eric Rubin, both in the Division of Immunology and Infectious Diseases at the Harvard School of Public Health. The candidate is trained in Infectious Diseases and has the long term goal of establishing an independent laboratory studying M. tuberculosis pathogenesis with a particular focus on mycobacterial interaction with the host immune response and vaccine development. The didactic component of this program involves courses in molecular biology and immunology through Harvard University. The research component of this program involves exploration of two putative mechanisms of immune evasion by M. tuberculosis, inhibition of IFN-gamma signaling and inhibition of inducible IL-12 production in infected macrophages. The specific aims of the research proposed will be: 1) to determine whether Toll-like receptor 2 (TLR-2) activation inhibits IFN-gamma signaling or inducible IL-12 production; 2) to identify the M. tuberculosis genes required for inhibition of IFN-gamma and IL-12 signaling by screening a transposon mutagenized library of M. tuberculosis; and 3) to characterize the genes identified in these screens.