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）：此P-RCE汇集了明尼苏达州，伊利诺伊州，密歇根州，印第安纳州和俄亥俄州的77位基础和临床研究人员的优势，以及大学和工业的优势。此应用程序的行政基础架构包括在所涉及的每个机构中的领导地位。我们的研究优势是A类生物恐怖，吸入生物学和宿主对A类生物体，诊断和实验疗法的宿主反应的基本生物学，以及疫苗评估，后者是我们有两个主要组织，他们有两个致力于参与的主要组织。我们对将基础研究转移到临床应用中特别感兴趣。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芽孢杆菌中新型的两组人调节系统，在其他革兰氏阳性细菌中对于毒力至关重要。我们已经表明，调节系统的同源物存在于炭疽芽孢杆菌中，并开始了以克隆和插入使系统失活的研究。此外，我们假设该调节系统是我们已经鉴定出并抑制外毒素产生的化合物的靶标。第二个R01提供了我们在吸入生物学方面的实力的一个例子，该项目旨在研究Francisella tularensis进入和贩运巨噬细胞的机制，以及在这些过程中表面活性剂的作用。概念项目补充了这些研究，并开始研究病毒剂。我们预计，在1 - 2年内，这些赠款将发展为3-4个计划项目。此外，我们已经组建了一支由高技能的领导者组成的团队，以在A类代理商的安全处理中培训现在和未来的研究人员。我们有大量的集体BSL3设施来实现这一培训，并结合了一个构想的计划。最后，我们已经开始与所有区域V州的一线应急人员进行无缝互动的发展，如果发生生物恐怖事件，我们的意图是作为溢出的“基准工人”。