Transcriptional analysis of the guinea pig model of tuberculosis

描述(申请人提供)：这项研究的目的是使用微阵列分析来更彻底地了解受感染的豚鼠对结核病的宿主反应，被广泛认为是这种疾病最相关的小动物模型。利用生物信息学，我们建议进一步探索这个动物模型中全球免疫反应的性质，包括临床相关的[高/低传播]W-Beijing结核分枝杆菌菌株，以及以前接种过疫苗的动物。我们特别感兴趣的是进一步研究新疫苗由于诱导宿主对高毒力的W-Beijing毒株做出反应的调节性T细胞网络而无效的可能性。在过去的一年里，我们的两个合作网站密切合作，解决了关于分离豚鼠肺RNA的各种技术问题，以及运输问题，我们现在有了一个可行的方案来基于这些研究[因此，也就是一些初步数据]。该计划是在CSU最先进的生物安全III级设施中为豚鼠接种疫苗并进行挑战，然后将分离的RNA发送到班加罗尔的Genypic进行进一步的微阵列分析。虽然这项技术不再是“新的”，但这将是第一次在豚鼠模型上进行，也是第一次在疫苗接种和结核病的特定背景下进行[从而使其对美国-印度疫苗行动计划倡议高度响应]。因此，在这个重要和相关的动物模型中，它有很高的潜力提供关于宿主反应的新信息。

DESCRIPTION (provided by applicant): The objective of this study is to use microarray analysis to more thoroughly understand the host response to tuberculosis in infected guinea pigs, widely regarded as the most relevant small animal model of this disease. Using bioinformatics, we propose to further probe the nature of the global immune response in this animal model, both to clinically relevant [high/low transmission] W-Beijing strains of M.tuberculosis, and in animals previously vaccinated. We are specifically interested in further examining the possibility that new vaccines will be ineffective due to the induction in the host of regulatory T cell networks that respond to the highly virulent W-Beijing strains. Over the past year our two collaborative sites have worked together closely to solve a variety of technical problems regarding isolation of guinea pig lung RNA, as well as transport issues, and we now have a workable protocol to base these studies on [and as a consequence, some preliminary data]. The plan is to vaccinate and challenge guinea pigs in the state of the art biosafety level-III facilities at CSU, then send isolated RNA to Genotypic in Bangalore for further analysis by microarray. While this technology is no longer "new" this will be the first time it has been done in the guinea pig model, and the first time in the specific context of vaccination and tuberculosis [thus making it highly responsive to the US-Indo Vaccine Action Program initiative]. As a result, it has high potential to provide new information about the host response in this important and relevant animal model.