Transcriptional analysis of the guinea pig model of tuberculosis

描述（由申请方提供）：本研究的目的是使用微阵列分析更彻底地了解感染豚鼠对结核病的宿主反应，该豚鼠被广泛认为是该疾病最相关的小动物模型。使用生物信息学，我们建议进一步探索该动物模型中的整体免疫应答的性质，包括临床相关的[高/低传播] W-北京结核分枝杆菌菌株和先前接种疫苗的动物。我们特别感兴趣的是，进一步研究新疫苗将是无效的可能性，由于在宿主中的调节性T细胞网络的诱导，响应于高毒力的W-北京菌株。在过去的一年里，我们的两个合作中心密切合作，解决了关于豚鼠肺RNA分离的各种技术问题，以及运输问题，我们现在有了一个可行的方案来建立这些研究[因此，一些初步数据]。该计划是在CSU最先进的生物安全三级设施中对豚鼠进行疫苗接种和挑战，然后将分离的RNA送到班加罗尔的基因型研究所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中进行，也是第一次在疫苗接种和结核病的特定背景下进行[因此，它对美国-印度疫苗行动计划倡议高度响应]。因此，它具有很高的潜力，提供新的信息，在这个重要的和相关的动物模型的主机响应。

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.