Microbial Pathogenesis and Host Inflammatory Responses

描述(申请人提供)：以治疗相关的方式解决传染病，需要了解导致疾病过程的微生物毒力因素，以及这些因素如何影响宿主的免疫和炎症反应，以确定临床结果。实现这一理解为临床相关的转化研究提供了一个完美的机会，也是我们建议的微生物致病和宿主炎症反应中心的首要主题。我们中心发展的关键要素是将有前途的年轻研究人员聚集在一起，每个人都在老牌高级教员的指导下，他们的研究与这一科学主题一致。将这些研究人员联系在一起的潜在假设是，在一个集成的、高度结构化的环境中针对不同的病原体和致病过程，将优化阐明与宿主反应及其对疾病过程的不利影响有关的共同主题的机会。为此，该应用程序将专注于病毒(Forrest)、细菌(Scurlock)和寄生虫(Stumhofer)病原体的初级研究人员聚集在一起，担任项目负责人。此外，根据研究表明，持续的病毒和细菌感染在许多慢性病的发展中起着关键作用，第四位研究员(Ortmann)将专注于炎症性关节炎的宿主反应，其中最主要的例子是类风湿性关节炎。我们建议(目标1)在潜在科学主题的背景下为年轻研究人员制定综合和互动的教师发展计划，近期目标是利用中心的资源使这些研究人员能够建立独立的研究生涯，并采取具体措施确保他们的成功没有行政或技术障碍；(目标2)加强阿肯色大学医学科学和阿肯色州儿童医院托管校区的生物医学研究基础设施；以及(目标3)在前两个目标的成功基础上，招聘更多的初级教师，并创建建立一个自我维持的生物医学卓越研究中心所需的协作和协同环境。作为进一步优化学术、实验和翻译协同的一种手段，还特别考虑了与东道国校园现有的NCRR资助项目的整合。其中包括阿肯色州INBRE，UAMS CTSA临床和翻译研究中心，以及Cobre成立的翻译神经科学中心。将所有这些要素结合在一起将提供一个综合和支持性的研究基础设施，这将显著提高项目负责人建立独立的、外部资助的研究计划的能力。长期目标是将此应用程序中包含的项目负责人与新招聘的初级调查人员以及能够显著扩展现有调查人员的现有调查人员进行整合 以符合基本科学主题的方式开展研究计划，以创造成功的计划项目应用所需的协作和翻译协同效应，并建立一个可影响人类健康的自给自足的翻译研究中心。

DESCRIPTION (provided by applicant): Addressing infectious disease in a therapeutically relevant fashion requires an understanding of both the microbial virulence factors that contribute to the disease process and how these factors impact the host immunological and inflammatory response to define the clinical outcome. Achieving this understanding provides a perfect opportunity for clinically relevant translational research and is the overriding theme of our proposed Center for Microbial Pathogenesis and Host Inflammatory Responses. The key element in the development of our Center is to bring together promising young investigators, each under the mentorship of established senior faculty, whose research is consistent with this scientific theme. The underlying hypothesis that ties these investigators together is that targeting diverse pathogens and pathogenic processes in an integrated, highly structured environment will optimize opportunities for the elucidation of common themes with respect to the host response and its adverse consequences on the disease process. To this end, this application brings together as Project Leaders junior investigators who focus on viral (Forrest), bacterial (Scurlock), and parasitic (Stumhofer) pathogens. Additionally, based on studies suggesting that persistent viral and bacterial infection plays a key role in the development of many chronic diseases, a fourth investigator (Ortmann) will focus on the host response in inflammatory arthritis, the principal example of which is rheumatoid arthritis. We propose to (Aim 1) enact an integrated and interactive faculty development plan for young investigators in the context of the underlying scientific theme with the immediate goal of leveraging the resources of the Center to enable these investigators to establish independent research careers and taking specific steps to ensure the absence of administrative or technical barriers to their success; (Aim 2) strengthen the biomedical research infrastructure on the host campuses of the University of Arkansas for Medical Sciences and Arkansas Children's Hospital; and (Aim 3) build on the success of these first two aims to recruit additional junior faculty and create the collaborative and synergistic environment required to establish a self-sustaining Center of Biomedical Research Excellence. As a means of further optimizing the academic, experimental, and translational synergy, specific consideration is also given to integration with existing NCRRfunded programs on the host campuses. These include the Arkansas INBRE, the UAMS CTSA Center for Clinical and Translational Research, and the Center for Translational Neuroscience, an established COBRE. Bringing all of these elements together will provide an integrated and supportive research infrastructure that will significantly enhance the ability of th Project Leaders to establish independent, extramurally funded research programs. The long-term goal is to integrate the Project Leaders included in this application with newly recruited junior investigators and with established investigators who can significantly expand their existing research programs in a manner consistent with the underlying scientific theme, to create the collaborative and translational synergy required for the development of successful program project applications and a self-sustaining translational research center that can impact human health.