Identifying Microorganisms involved in Human Health and Disease Processes

描述(申请人提供)：微生物在人类生物学中扮演着各种重要的角色。它们合成维生素，抑制病原体，调节脂肪储存和免疫系统，并导致癌症和传染病。尽管有这些重要的发现，但我们对微生物在人类生物学中的作用的整体理解仍处于初级阶段。这一领域的进展缓慢是由于目前用于研究微生物群落的方法的局限性，包括产量不足和成本高。该提案的具体目标是通过开发新的高通量方法和软件来解决这些限制。特别是，我们将开发(1)高通量、基于rRNA基因的方法来识别微生物，(2)表征特定微生物水平与健康或疾病过程之间的关联的新方法，以及(3)支持这些实验过程并使其自动化的集成软件套件。具体目标(4)是进行全面的测试，以验证我们的方法，并与其他方法相比评估它们的实用性。这些新的实验能力将使我们能够解决我们研究的长期目标，即了解微生物在炎症性肠病(IBD)的病因学以及人类粘膜免疫的发展和动态平衡中的作用。它们还将使旨在识别参与其他人类健康和疾病过程的微生物的无数调查成为可能。该项目通过利用跨学科研究团队开发创新的分子、计算和统计方法来研究微生物在人类健康和疾病过程中的作用，从而实现了NIH路线图和PA“生物医学计算科学和技术的创新”的使命。我们的工作结果可能会影响微生物学以外的领域，因为所提出的方法和软件可能在微阵列数据分析、基于指纹的分类研究和其他研究领域被证明是有用的。公共卫生相关性：我们建议开发新的实验方法来研究微生物在粘膜免疫、IBD和其他人类健康和疾病过程中的作用。这些新工具将导致新的战略，以预防、管理或治愈IBD，以及与微生物相关的多种其他疾病。

DESCRIPTION (provided by applicant): Microorganisms play a variety of important roles in human biology. They synthesize vitamins, inhibit pathogens, modulate fat storage and the immune system, and cause cancers and infectious diseases. Despite these important findings, our overall understanding of the microbial role in human biology is still in its infancy. Slow progress in this area is caused by limitations of the currently used methods for studying microbial communities, including insufficient throughput and high cost. The Specific Aims of this proposal address these limitations through the development of new high- throughput methods and software. In particular, we will develop (1) a high-throughput, rRNA gene based method to identify microorganisms, (2) novel approaches to characterize the associations between levels of specific microorganisms and health or disease processes, and (3) an integrated software suite to support and automate these experimental processes. Specific Aim (4) is to perform comprehensive tests to validate our methods and evaluate their utility in comparison to other approaches. These new experimental capabilities will enable us to address the long-term objective of our research, which is to understand the role of microorganisms in the etiology of inflammatory bowel disease (IBD) and in the development and homeostasis of mucosal immunity in humans. They will also enable a myriad of investigations aimed at identifying microorganisms involved in other human health and disease processes. This project addresses the mission of the NIH Roadmap and the PA "Innovations in Biomedical Computational Science and Technology" by utilizing an interdisciplinary research team to develop innovative molecular, computational, and statistical methods for studying the roles of microorganisms in human health and disease processes. The results of our work are likely to impact areas outside of microbiology, as the proposed methods and software could prove useful in microarray data analysis, fingerprint-based taxonomic studies, and other fields of research. PUBLIC HEALTH RELEVANCE: We propose to develop new experimental approaches to investigate the role of microorganisms in mucosal immunity, IBD and other human health and disease processes. These new tools should lead to new strategies to prevent, manage or cure IBD, as well as the multitude of other diseases associated with microorganisms.