Analysis of a reaeration model of latent TB reactivation

描述(申请人提供)：拟议的博士后研究的目标是利用体外低氧模型表征结核分枝杆菌从休眠状态重新激活的遗传程序。对这些基因重新激活的要求将通过突变和体外和体内表型评估来测试。这项研究将提高我们对结核分枝杆菌潜伏状态和随后重新激活的细菌生理学的理解。该项目的具体目标是： 1.采用体外模型，通过微阵列分析鉴定再激活特异性基因。 2.利用转座子位点杂交技术(Trash)鉴定低氧休眠向复氧培养转化所必需的基因。 3.分离插入预测再激活特异性基因的转座子突变体，并在体外和小鼠模型中测试对这些基因重新激活的需求。

DESCRIPTION (provided by applicant): The goal of the proposed postdoctoral research is characterize the genetic program of reactivation from dormancy in Mycobacterium tuberculosis using an in vitro hypoxic model. The requirement for these genes in reactivation will be tested by mutagenesis and in vitro and in vivo phenotypic assessment. This investigation will improve our understanding of the bacterial physiology of M. tuberculosis in the latent state and subsequent reactivation. The specific aims of the project are: 1. To use an in vitro model to identify reactivation-specific genes using microarray analysis. 2. To identify genes essential for the transition from hypoxic dormancy to reaerated culture using transposon site hybridization (TraSH). 3. To isolate transposon mutants with insertions into predicted reactivation-specific genes and to test the requirement for these genes for reactivation in vitro and in a mouse model.