Transcriptional analysis of the guinea pig model of tuberculosis

豚鼠结核病模型的转录分析

基本信息

批准号：
8594218
负责人：
IAN M ORME
金额：
$ 6.42万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-10 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8594218
关键词：
Aerosols Animal Disease Models Animal Model Animals Antigens Basic Science Bioinformatics Cavia Clinical Collaborations Colorado DNA Microarray Chip Data Disease Dose Event Exhibits Family Flow Cytometry Funding Genes Genomics Genus Mycobacterium Gold Human Immune response India Infection Laboratories Laboratory Research Learning Lung Memory Methods Microarray Analysis Modeling Mycobacterium tuberculosis Nature Necrosis Organism Pathology Process Protocols documentation RNA Reagent Regulatory T-Lymphocyte Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Site Technology Testing Time Translational Research Tuberculosis Tuberculosis Vaccines Universities Vaccinated Vaccination Vaccines Virulent Work base clinically relevant design immunopathology interest new technology novel novel vaccines optimism pandemic disease pig genome prevent programs protective effect public health relevance rBCG transmission process vaccination against tuberculosis vaccine candidate

项目摘要

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.

描述（由申请人提供）：本研究的目的是使用微阵列分析，以更彻底地了解受感染的豚鼠对结核病的宿主反应，被广泛认为是该疾病中最相关的小动物模型。使用生物信息学，我们建议在该动物模型中进一步探测全球免疫反应的性质，包括临床相关[高/低传播] W-Beijing M.tuborculculosis，以及先前接种疫苗的动物。我们特别有兴趣进一步研究新疫苗将由于对高度毒性的W-北京菌株反应的监管T细胞网络的诱导诱导而无效的可能性。在过去的一年中，我们的两个协作站点已密切合作，以解决有关差异豚鼠肺RNA以及运输问题的各种技术问题，我们现在拥有一项可行的协议，可以基于这些研究[以及结果，而某些初步数据]。该计划是在CSU最先进的生物安全水平III设施状态下疫苗接种和挑战豚鼠，然后将孤立的RNA发送到班加罗尔的基因型，以通过微阵列进行进一步分析。尽管这项技术不再是“新”，但这将是豚鼠模型中的第一次，也是第一次在疫苗接种和结核病的具体情况下[从而使其对美国 - 印度疫苗疫苗行动计划计划的反应迅速]。结果，在这个重要且相关的动物模型中提供有关宿主反应的新信息具有很高的潜力。