Microbial Pathogenesis and Host Inflammatory Responses

微生物发病机制和宿主炎症反应

• 批准号: 8216491
• 负责人: MARK S SMELTZER
• 金额: $ 198.28万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8216491
• 关键词: Address; Antibiotic Resistance; Antimicrobial Resistance; Arkansas; Bacterial Infections; Biomedical Research; Center for Translational Science Activities; Centers of Research Excellence; Chronic; Chronic Disease; Clinical; Clinical Research; Communicable Diseases; Complex; Core Facility; Data Analyses; Development; Development Plans; Disease; Elements; Ensure; Environment; Faculty; Failure; Foundations; Funding; Goals; Grant; Health; Human; Immune response; Indium; Infection; Inflammatory Response; Medical; Mentors; Mentorship; National Center for Research Resources; Outcome; Pathogenesis; Pathology; Pediatric Hospitals; Play; Process; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Rheumatoid Arthritis; Science; Scientist; Structure; TNFRSF5 gene; Translational Research; Universities; Viral; Virulence Factors; Virus Diseases; adverse outcome; antimicrobial drug; base; career; clinically relevant; interest; medical specialties; microbial; pathogen; programs; public health relevance; success; translational neuroscience

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.

描述（由申请人提供）：以治疗相关的方式解决传染病，需要了解对疾病过程促成疾病过程的两个微生物毒力因素，以及这些因素如何影响宿主的免疫学和炎症反应来定义临床结果。实现这一理解为临床相关的翻译研究提供了绝佳的机会，是我们提议的微生物发病机理和宿主炎症反应中心的重要主题。我们中心发展的关键要素是将有前途的年轻调查员汇集在一起​​，每个研究人员在既定的高级教师的指导下，其研究与这个科学主题一致。将这些研究者联系在一起的基本假设是，在综合，高度结构化的环境中靶向多种病原体和致病过程将优化阐明共同主题在宿主反应及其对疾病过程的不利后果的机会。为此，该应用程序汇集了项目领导者的初级研究人员，他们专注于病毒（Forrest），细菌（Scurlock）和寄生虫（Stumhofer）病原体。此外，基于研究表明持续性病毒和细菌感染在许多慢性疾病的发展中起关键作用，第四个研究者（ORTMANN）将重点介绍炎症性关节炎的宿主反应，其主要例子是类风湿关节炎。我们建议（AIM 1）在基本的科学主题的背景下为年轻研究人员制定一项综合互动的教师发展计划，其直接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职业，并采取具体步骤，以确保缺乏行政或技术障碍来取得成功； （AIM 2）在阿肯色大学医学科学和阿肯色州儿童医院的主持校园内加强生物医学研究基础设施； （AIM 3）建立在前两个旨在招募其他初级教师并创建建立自我维持生物医学研究卓越中心所需的协作和协同环境的成功基础上。作为进一步优化学术，实验和翻译协同作用的一种手段，还考虑了与主机校园中现有的NCRRFUND计划集成的特定考虑。其中包括阿肯色州INBRE，UAMS CTSA临床和转化研究中心，以及已建立的毛病转化神经科学中心。将所有这些要素汇集在一起​​将提供一个集成和支持性的研究基础设施，从而大大提高项目领导者建立独立的，外部资助的研究计划的能力。长期的目标是将本申请中的项目负责人与新招聘的初级调查员以及既定的调查员进行整合，他们可以大大扩展其现有的现有 研究计划的方式与基本的科学主题一致，以创建成功的计划项目应用程序所需的协作和转化协同作用，并建立可能影响人类健康的自我维持的转化研究中心。