MWCE: Transmission/Pathogenesis of Bioterrorism Agents

MWCE：生物恐怖主义制剂的传播/发病机制

• 批准号: 6698883
• 负责人: Patrick M Schlievert
• 金额: $ 68.31万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-04 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6698883
• 关键词: Bacillus anthracis; bioterrorism /chemical warfare; clinical research; tularemia; vaccine evaluation

DESCRIPTION (provided by applicant): This P-RCE brings together the strengths of 77 researchers, both basic and clinical and from both Universities and Industry, in the states of Minnesota, Illinois, Michigan, Indiana, and Ohio. Administrative infrastructure for this application includes leadership at each one of the institutions involved. Our research strengths are in Basic Biology of Category A agents of Bioterrorism, Inhalation Biology and Host Response to Category A organisms, Diagnostics and Experimental Therapeutics, and Vaccine Evaluation, the latter where we have two premier organizations committed to participate. We are particularly interested in moving basic research into clinical application. We submit two R01s and several concept projects in these areas. The first R01 seeks funding to study a novel two-component regulatory system in Bacillus anthracis that in other Gram-positive bacteria is essential to virulence. We have shown that the regulatory system homologue exists in B. anthracis and have initiated studies to clone and insertionally inactivate the system. Furthermore, we hypothesize that this regulatory system is the target of compounds that we have identified and inhibit production of exotoxins. The second R01 provides an example of our strength in Inhalation Biology with a project to study the mechanism underlying Francisella tularensis entry and trafficking into macrophages, and the role surfactant plays in these processes. Concept projects complement these studies and initiate research into Category A viral agents. We anticipate that in 1-2 years these grants will develop into 3-4 program projects. In addition, we have assembled a team of highly-skilled leaders to train both present and future researchers in the safe handling of Category A agents; we have a large collective number of BSL3 facilities to achieve this training, combined with a well-conceived plan. Finally, we have begun development of seamless interactions with first-line emergency responders in all Region V states, with our intent to serve as overflow "Bench Workers" if bioterrorism events occur.

描述（由申请人提供）：该 P-RCE 汇集了来自明尼苏达州、伊利诺伊州、密歇根州、印第安纳州和俄亥俄州的 77 名基础研究人员和临床研究人员以及来自大学和工业界的研究人员的优势。该应用程序的管理基础设施包括所涉及的每个机构的领导。我们的研究优势在于生物恐怖主义 A 类制剂的基础生物学、吸入生物学和宿主对 A 类生物体的反应、诊断和实验治疗学以及疫苗评估，后者是我们有两个主要组织承诺参与的领域。我们特别有兴趣将基础研究转化为临床应用。我们在这些领域提交了两个 R01 和几个概念项目。第一个 R01 寻求资金来研究炭疽杆菌中的一种新型双组分调节系统，该系统在其他革兰氏阳性细菌中对于毒力至关重要。我们已经证明炭疽芽孢杆菌中存在调节系统同源物，并已启动克隆和插入灭活该系统的研究。此外，我们假设该调节系统是我们已识别并抑制外毒素产生的化合物的目标。第二个 R01 提供了一个例子，展示了我们在吸入生物学方面的实力，该项目旨在研究土拉弗朗西斯菌进入和运输到巨噬细胞的机制，以及表面活性剂在这些过程中发挥的作用。概念项目补充了这些研究，并启动了对 A 类病毒制剂的研究。我们预计这些赠款将在 1-2 年内发展成 3-4 个计划项目。此外，我们还组建了一支高技能领导团队，对当前和未来的研究人员进行安全处理 A 类药剂的培训；我们拥有大量的 BSL3 设施来实现这一培训，并结合了周密的计划。最后，我们已经开始与第五区所有州的一线应急响应人员建立无缝互动，我们的目的是在发生生物恐怖主义事件时充当溢出的“替补工作人员”。