M tuberculosis evasion of the innate immune response

描述(由申请人提供)：这份建议书描述了一项为期五年、为期两年的计划 结核分枝杆菌研究的职业发展计划。 这项计划将在巴里·布鲁姆博士的实验室与 埃里克·鲁宾博士在免疫学部和 哈佛大学公共卫生学院的传染病。候选人是 受过传染病方面的培训，并有建立一支 独立实验室研究结核分枝杆菌的发病机制 关注分枝杆菌与宿主免疫反应和疫苗的相互作用 发展。该计划的教学部分包括以下课程 哈佛大学分子生物学和免疫学。这项研究 这一计划的组成部分包括探索两种可能的机制 结核分枝杆菌的免疫逃避，干扰素-γ信号的抑制和 抑制感染巨噬细胞诱导性IL-12的产生。具体的 提出的研究目标将是：1)确定类似于收费的 受体2(TLR-2)的激活抑制干扰素-γ信号或诱导的IL-12 生产；2)鉴定抑制结核分枝杆菌所需的基因 通过筛选转座子诱变文库研究干扰素-γ和白介素12信号转导 结核分枝杆菌；以及3)确定这些基因的特征 屏幕。

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.