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)：这个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名基础和临床研究人员的力量，以及来自大学和工业界的研究人员。此应用程序的行政基础设施包括所涉及的每个机构的领导力。我们的研究优势是A类生物恐怖主义制剂的基础生物学、A类生物的吸入生物学和宿主反应、诊断和实验治疗学以及疫苗评估，后者是我们承诺参与的两个主要组织。我们对将基础研究转化为临床应用特别感兴趣。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，以研究炭疽芽孢杆菌中的一种新的双组分调控系统，该系统在其他革兰氏阳性细菌中是毒力必不可少的。我们已经证明在炭疽杆菌中存在调节系统同源物，并已开始研究克隆和插入失活该系统。此外，我们假设这个调控系统是我们已经识别并抑制外毒素产生的化合物的目标。第二个R01提供了我们在吸入生物学方面的优势的一个例子，该项目研究图拉氏方济氏菌进入和转运到巨噬细胞的机制，以及表面活性物质在这些过程中所起的作用。概念项目补充了这些研究，并启动了对A类病毒剂的研究。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，我们还组建了一支高技能的领导者团队，对目前和未来的研究人员进行安全处理A类特工的培训；我们拥有大量的BSL3设施来实现这一培训，并结合一个精心设计的计划。最后，我们已经开始与V地区所有州的第一线应急人员发展无缝互动，我们的意图是在发生生物恐怖主义事件时充当溢出的“板凳工人”。