Genome wide investigations of Mycobacterium tuberculosis to reveal processes of pathogenesis

结核病仍然是全球健康的一个巨大负担。大约三分之一的人感染了结核分枝杆菌，这是导致这种疾病的有机体，每年造成200万人死亡。现在出现的菌株对我们几乎所有的一线药物都有抗药性，这给那些试图开发新的保护性疫苗和根除这种疾病所需的关键抗生素的研究人员带来了额外的压力。此外，目前全球艾滋病毒流行病使情况更加恶化，因为艾滋病毒杀死了保护我们免受结核病侵害的身体细胞。这项研究项目将填补我们对M.结核病感染，特别是确定基因的有机体，使它能够入侵和蔓延到整个身体。M.结核病感染包括三个特征性阶段，即在称为肉芽肿的专门结构中的定殖、扩散和长期存活。正是从这些肉芽肿中，细菌可以在长时间不活动后出现，引起临床结核病。使用小鼠感染模型，我将确定细菌在疾病的这三个关键阶段生存所需的基因，从而提供更好的知识基础，以设计新的疫苗策略和创造有效的药物。

Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is making the situation far worse as HIV kills the very cells of the body that protect us from tuberculosis. This research project will fill the significant gaps in our knowledge of M. tuberculosis infection, specifically identify the genes of the organism which allow it to invade and spread throughout the body. M. tuberculosis infection consists of 3 characteristic stages, i.e. colonisation, spread and long term survival in specialised structures called granulomas. It is from these granulomas that the bacterium can emerge after long periods of inactivity to cause clinical tuberculosis. Using a mouse model of infection I will define the genes needed by the bacterium to survive at these 3 key stages of disease thereby providing for a better knowledge base from which to design new vaccine strategies and to create effective drugs.