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：
8240633
负责人：
IAN M ORME
金额：
$ 7.63万
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 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8240633
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）：本研究的目的是利用微阵列分析来更彻底地了解受感染豚鼠的宿主对结核病的反应，豚鼠被广泛认为是该疾病最相关的小动物模型。我们建议利用生物信息学，进一步探讨该动物模型中针对临床相关的[高/低传播]结核分枝杆菌W-北京菌株以及先前接种疫苗的动物的整体免疫反应的性质。我们特别感兴趣的是进一步研究新疫苗因宿主中对高毒力 W-Beijing 毒株作出反应的调节性 T 细胞网络的诱导而无效的可能性。在过去的一年里，我们的两个合作中心密切合作，解决了有关豚鼠肺 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基础这些研究 [并因此，一些初步数据]。该计划是在科罗拉多州立大学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 发送到班加罗尔的 Genotypic 进行进一步的微阵列分析。虽然这项技术不再是“新技术”，但这将是第一次在豚鼠模型中完成，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-印度疫苗行动高度敏感计划倡议]。因此，它很有可能在这一重要且相关的动物模型中提供有关宿主反应的新信息。