New Opportunity

新机遇

• 批准号: 7942437
• 负责人: WILL GILLETT
• 金额: $ 23.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-20 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7942437
• 关键词: Advisory Committees; Alaska; Animal Model; Animals; Applications Grants; Area; Asia; Automobile Driving; Award; Bacteria; Baltimore; Basic Science; Bioinformatics; Biological; Biology; Biomedical Research; Biotechnology; British Columbia; Burkholderia pseudomallei; Canada; Categories; Centers for Disease Control and Prevention (U.S.); Centers of Research Excellence; Child; Cities; Clinical; Collaborations; Collection; Communicable Diseases; Communication; Communities; Complement; County; Data; Databases; Department of Defense; Development; Disease; Disease Outbreaks; Disease Outcome; Elements; Emergency Situation; Emerging Communicable Diseases; Environment; Evaluation; Event; Experimental Models; Faculty; Fostering; Foundations; Francisella; Francisella tularensis; Funding; Genomics; Genotype; Goals; Gram-Negative Bacteria; Grant; Growth; Health; Health Sciences; Housing; Human; Human Resources; Idaho; Infection; Infectious Diseases Research; Influenza A Virus, H5N1 Subtype; Institutes; Institution; International; Intramural Research; Joints; Justice; Knowledge; Laboratories; Lead; Leadership; Letters; Libraries; Malignant Neoplasms; Maryland; Medical center; Melioidosis; Methodology; Metric; Mexican; Mexico; Microbiology; Modernization; Montana; Moscow; Mouse Strains; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences; Northern Europe; Nuclear; Oregon; Pacific Northwest; Pathogenesis; Pathology; Pharmaceutical Chemistry; Phase; Phenotype; Private Sector; Program Development; Proteomics; Pseudomonas aeruginosa; Public Health; Research; Research Infrastructure; Research Institute; Research Personnel; Research Priority; Research Project Grants; Research Training; Resources; Risk; Scientist; Screening procedure; Shigella dysenteriae; Site; Source; Structure; Sweden; System; Systems Biology; Technology; Terrorism; Thailand; Therapeutic; Transgenic Mice; Translating; Translational Research; Translations; United States; United States National Institutes of Health; United States Public Health Service; Universities; Variant; Vector-transmitted infectious disease; Virginia; Washington; Work; antimicrobial; benefit sharing; biodefense; biosafety level 3 facility; cystic fibrosis patients; design; experience; flexibility; genome sequencing; instrumentation; medical schools; meetings; member; mutant; new technology; outreach; pandemic influenza; pathogen; product development; programs; repository; response; small molecule libraries; sound; vaccine candidate

2.b. Opportunities The NWRCE is primed to produce high quality research, training, and development programs in the biology of Gram-negative bacteria relevant to biodefense and emerging infectious diseases. During the first grant period, the Center has become an efficient engine of basic science, translational research, and product development. As a new program, the RCEs underwent a natural startup phase, but this period is now over and the NWRCE has implemented all its functional elements. Using a combination of modern technologies, new knowledge of basic mechanisms of bacterial pathogenesis, and the wide availability of genome sequences, the NWRCE is capable of driving infectious disease research at a rapid pace. By using a high throughput approach in which large amounts of relevant data can be quickly generated, assessed for potentially practical benefits, and shared among a consortium of skilled investigators, the NWRCE is designed to produce knowledge and products of practical benefit to infectious diseases of national significance. Growth of the NWRCE at the University of Washington would further capitalize on the vibrant and expanding research environment at the UW. The University of Washington is one of the most best-funded public biomedical research institutions in the nation, and the research infrastructure is continuing to undergo expansion. The UW is creating new research space at its South Lake Union site in Seattle, which includes BSL-3 facilities. This space could potentially be used for recruitments in new research areas that would add additional strength, capacity, and flexibility to the NWRCE. Recently, the new Department of Global Health was formed, chaired by King Holmes who serves on the NWRCE External Advisory Board. Large-scale renovation projects in the Health Sciences Building, which houses the Select Agent Laboratory and a number of Center investigators, are underway as part of a multi-year program of research space modernization. Seattle is a unique environment with many institutions including the Gates Foundation, Program for Appropriate Technology in Health (PATH), Infectious Disease Research Institute (IDRI), the Institute for Systems Biology (ISB), Seattle Biomedical Research Institute (SBRI) Virginia Mason Reseach Center, the Fred Hutchinson Cancer Centter, as well as the University of Washington, all of which make infectious diseases and immunological responses to pathogens a major research priority. The NWRCE has the opportunity to further develop collaborations with regional, national, and international entities. As described in the Overview, the NWRCE has investigators and collaborators affiliated with the following participating institutions: ¿ University of Washington School of Medicine Seattle, WA ¿ VA Puget Sound Medical Center, Seattle WA ¿ Harborview Medical Center, Seattle, WA ¿ The Institute for Systems Biology, Seattle, WA ¿ Children's Regional Medical Center, Seattle, WA ¿ NIAID Rocky Mountain Laboratories, Hamilton, MT ¿ University of Idaho, Moscow, ID ¿ University of Oregon, Eugene, OR ¿ Oregon Health & Sciences University, Portland, OR ¿ University of Maryland, Baltimore, MD ¿ University of Louisville, Louisville, KY ¿ Public Health Seattle/King County ¿ University of Victoria, British Columbia, Canada ¿ Mahidol University, Bangkok, Thailand ¿ Umea University, Umea, Sweden ¿ Institute de Diagnostico y Referenda Epidemiologicos, Mexico City, Mexico There are a number of other entities in Region X which provide further opportunities for interactions with the NWRCE, including the previously mentioned Department of Global Health, the Institute for Health Metrics and Evaluation, and the Gates Foundation. The NWRCE has previously sponsored developmental projects at the University of Alaska-Fairbanks and Oregon State University and will continue these outreach efforts. External Advisory Board member Guy Palmer is appointed at Washington State University in Pullman, WA, and the Directors have also interacted with Washington State University Veterinary Microbiology & Pathology faculty member Dr. Thomas E. Besser. These interactions will be strengthened for the purposes of adding zoonotic disease expertise to the NWRCE. The three foreign institutions listed above comprise the NWRCE's foreign collaborators. Established during the supplemental year, these collaborations provide access to international strain collections, clinical information, and expertise from endemic areas. Dr. Sharon Peacock with Mahidol University will be working with NWRCE investigators to provide an extensive clinical repository of Burkholderia pseudomallei as well as her scientific expertise as a noted researcher on melioidosis, the disease caused by B. pseudomallei. Dr. Anders Sjostedt of Umea University will provide isolates of Francisella from northern Europe and Asia. Dr. Celia Alpuche Aranda of the Institute de Diagnostico y Referenda Epidemiologicos (the Mexican equivalent of the US Centers for Disease Control and Prevention) will provide strains and clinical information from current and historic outbreaks of Shigella dysenteriae and other emerging and outbreak-related Gram-negative strains. These collaborations will increase the profile of the NWRCE and the RCE network internationally, and potentially foster additional interactions with other officials and investigators at these international sites of relevance to disease emergence on the West Coast of the United States. These strains from foreign sites will be utilized extensively by multiple projects, and will provide a reference source for comparison of new outbreaks, either naturally occurring or man-made, and as such will contribute to our emergency response capacity. The NWRCE will expand its interactions with federal agencies, intramural research laboratories, state and local health departments, and the private sector. As a result of the research emphasis on infectious disease, select agents, and national biodefense needs, NWRCE Directors and Investigators have access to and a working dialogue with federal officials and agencies, and have, over the past five years, advised and interacted with officials from the Department of Justice, Department of Defense, Public Health Service, USDA, FDA, CDC, and the Executive Branch. Examples of such interactions include meeting with Colonel Ralph Erickson, Director of GEIS (Global Emerging Infections System DoD), participating in a Defense Threat Reduction Agency subcontract (HDTRA-07-9-0003), and attending briefings by Joint Terrorism Task force agents (FBI/DoJ). The Emergency Response Director has advised the White House on the impact of a possible H5N1 flu pandemic. The NWRCE Director also participated in a meeting advising the FBI on its relationship with academic institutions with respect to nuclear, technological and biological threat risk. The Directors have had communication with Dick Smith of the Pacific Northwest National Laboratories (PI of High Throughput Proteomics), and will continue to explore ways in which the PNNL and the NWRCE may interact. A number of NWRCE personnel, most notably Emergency Response director Jeff Duchin MD, have CDC experience and have facilitated communication with that agency on several occasions. Dr. Duchin also has extensive connections in the regional public health sector as Chief of Communicable Diseases for Public Health - Seattle & King County. He has helped to facilitate contact with public health laboratories in the city, state, region, and nation. Additionally, the NWRCE has participated in several grant applications with biotechnology companies (Implicit Biosciences and Micronics, Inc.). In both of these cases the NWRCE was sought out because of its select agent capabilities and expertise. These interactions have been quite fruitful and will likely increase as the Center moves into new research areas, adds new investigators, and moves products into development. The NWRCE will expand its capacity to form part of a national resource in proteomics, genomics, and bioinformatics for the study of Gram-negative infections. The NWRCE created capacity in these methodologies and applied them to the study of basic science, proteomics, and genomic aspects of Gramnegative bacteria. This effort has produced information and databases of use to biodefense/EID researchers, and infectious disease investigators in general. The NWRCE will continue to use its specific focus and economy of scale to integrate the data from throughout the infectious disease field, the biodefense network, and its own research findings to increase its value as a resource. Efforts such as these can best be catalyzed and funded through a cooperative mechanism such as the national RCEs. In addition, the physical resources generated by NWRCE research (instrumentation, mutant libraries, chemical compound screening & libraries, and unique transgenic mouse strains) will enhance and accelerate research outside of the Center. The NWRCE will function in a complementary fashion with other efforts in the region to promote national research efforts in biodefense and emerging infectious diseases. Within Region X, over a billion dollars in NIH funding is currently awarded. NIAID alone sponsors 315 research grants in Washington, Oregon, Idaho, and Alaska, and 44 of them are awarded for study of NIAID Category A - C Priority Pathogens. NIH funding for infectious disease research is also granted to researchers through other institutes, such as NHLBI, NIDDK, and NIGMS. This scientific community combines to create a nationally significant infrastructure of infectious disease centered on the University of Washington. Another significant ongoing effort is the bacterial pathogenesis work being done at Rocky Mountain Laboratories in Montana. The NWRCE has established collaborations with two investigators at this NIH/NIAID facility, Dr. Joe Hinnebusch and Dr. Jean Celli, providing expertise and experimental models for V. peso's and F. tularensis, respectively. This laboratory is completing renovations to create BSL-4 laboratories; although the NWRCE has no current plans to study Risk Group 4 agents, these facilities may be available in such an event. This collaboration provides an excellent opportunity for cooperative, coordinated research with the scientists and facilities at RML. The strengths of RML in both Gram-negative and Gram-positive infections and vector borne diseases complement the efforts of the NWRCE, and an ongoing relationship between the institutions would create benefits for both (see Letters of Support). The NWRCE will continue to translate basic biological information into useful therapeutics and other countermeasures. The NWRCE is structured to allow rapid translation of basic discoveries into practical therapeutics. In the first grant period, the center advanced two vaccine candidates to animal trials and has advanced several lead antimicrobial compounds. In response to NIAID program requirements, this application refocuses the product development program toward the creation of therapeutics that function across a broad host range. These programs are already primed in terms of biological target identification, compound screening & medicinal chemistry, and animal models of efficacy. The NWRCE will become an important resource and maintain databases of information about currently active bacterial pathogens and begin to understand pathogen diversity and the diversity of human responses to these pathogens. The challenge for the 21st century is to understand and integrate pathogen and human diversity to understand and predict infectious disease outcomes. It is a goal of the NWRCE - and in part its raison d'etre - to begin this effort and provide leadership in this area. Drs. Olson and Miller have been leaders in defining genotypes and phenotypes of natural isolates of P. aeruginosa from cystic fibrosis patients. Dr. Aderem, Martin, Wilson, Hajjar, Ernst, Miller, and Wurfel have been among the leaders defining variation in human responses to Gram-negative agents.

2.b. 机会 NWRCE 已准备好在以下领域开展高质量的研究、培训和发展项目： 与生物防御和新出现的传染病相关的革兰氏阴性细菌的生物学。 在第一个资助期内，该中心已成为基础科学、转化研究和研究的高效引擎。 作为一个新项目，RCE 经历了一个自然的启动阶段，但现在这个阶段已经到来。 NWRCE 已使用现代技术的组合来实现其所有功能元素。 技术、细菌发病机制基本机制的新知识以及广泛可用的 通过使用基因组序列，NWRCE 能够快速推动传染病研究。 高通量方法，可以快速生成大量相关数据，并对其进行评估 NWRCE 的设计具有潜在的实际效益，并由熟练的研究人员组成的联盟共享 生产对具有国家意义的传染病有实际益处的知识和产品。 华盛顿大学 NWRCE 的发展将进一步利用充满活力和 华盛顿大学不断扩大的研究环境是资金最充足的大学之一。 国家的公共生物医学研究机构，研究基础设施正在持续改进 华盛顿大学正在西雅图的南湖联盟基地创建新的研究空间，其中包括。 BSL-3 设施可能会用于新研究领域的招募。 最近，新成立的全球卫生部为 NWRCE 增添了力量、能力和灵活性。 成立，主席为 King Holmes，他是 NWRCE 外部顾问委员会成员。 健康科学大楼内的项目，其中设有选择剂实验室和多个中心 西雅图是一个多年研究空间现代化计划的一部分。 独特的环境，拥有许多机构，包括盖茨基金会、适当项目 健康技术 (PATH)、传染病研究所 (IDRI)、系统生物学研究所 (ISB)、西雅图生物医学研究所 (SBRI) 弗吉尼亚梅森研究中心、弗雷德·哈钦森 (Fred Hutchinson) 癌症中心以及华盛顿大学，所有这些机构都研究传染病和 对病原体的免疫反应是一个主要的研究重点。 NWRCE 有机会进一步发展与地区、国家和地区的合作 国际实体。 如概述中所述，NWRCE 的研究人员和合作者隶属于以下机构： 参与机构： ¿华盛顿大学医学院 华盛顿州西雅图 ¿ VA 普吉特湾医疗中心，华盛顿州西雅图 ¿华盛顿州西雅图港景医疗中心 ¿系统生物学研究所，西雅图，华盛顿州 ¿华盛顿州西雅图儿童区域医疗中心 ¿ NIAID 落基山实验室，汉密尔顿，MT ¿爱达荷大学，莫斯科，爱达荷州 ¿俄勒冈大学，尤金，俄勒冈州 ¿俄勒冈健康与科学大学，俄勒冈州波特兰 ¿马里兰大学，巴尔的摩，马里兰州 ¿路易斯维尔大学，路易斯维尔，肯塔基州 ¿公共卫生西雅图/金县 ¿加拿大不列颠哥伦比亚省维多利亚大学 ¿泰国曼谷玛希隆大学 ¿于默奥大学，于默奥，瑞典 ¿流行病学诊断和参考研究所，墨西哥墨西哥城 X 区还有许多其他实体，它们提供了与 X 区进一步互动的机会 NWRCE，包括前面提到的全球卫生部、健康指标研究所和 评估和盖茨基金会此前曾赞助过该项目的开发项目。 阿拉斯加大学费尔班克斯分校和俄勒冈州立大学将继续开展这些外部推广工作。 顾问委员会成员 Guy Palmer 被任命为位于华盛顿州普尔曼的华盛顿州立大学的顾问委员会成员 董事们还与华盛顿州立大学兽医微生物学和病理学教师进行了互动 成员 Thomas E. Besser 博士将加强这些互动，以增加人畜共患病的数量。 向 NWRCE 提供疾病专业知识。 上述三个外国机构是NWRCE 的外国合作者。 在补充年中，这些合作提供了获得国际菌株收藏、临床 来自玛希隆大学的 Sharon Peacock 博士将提供信息和专业知识。 与 NWRCE 研究人员合作，提供广泛的鼻疽伯克霍尔德氏菌临床资料库以及 她作为类鼻疽（一种由类鼻疽杆菌引起的疾病）的著名研究员，拥有丰富的科学知识。 于默奥大学的 Anders Sjostedt 博士将提供来自北欧和亚洲的弗朗西斯菌分离株。 Celia Alpuche Aranda，来自流行病学诊断和全民公决研究所（墨西哥同等机构） 美国疾病控制和预防中心）将提供当前的菌株和临床信息 志贺氏菌和其他新出现的和与爆发相关的革兰氏阴性菌株的历史性爆发。 这些合作将提高 NWRCE 和 RCE 网络的国际知名度，并且 可能会促进与这些国际地点的其他官员和调查人员的更多互动 这些来自外国地点的菌株将与美国西海岸的疾病出现相关。 主要被多个项目使用，并将为新的比较提供参考来源 自然发生的或人为的爆发，因此将有助于我们的应急响应 容量。 NWRCE 将扩大与联邦机构、校内研究实验室、州政府的互动 以及地方卫生部门和私营部门由于研究重点是传染病。 疾病、选择药剂和国家生物防御需求，NWRCE 主任和研究人员可以获取 并与联邦官员和机构进行工作对话，并在过去五年中提供了建议和建议 与司法部、国防部、公共卫生服务部、美国农业部的官员进行互动， FDA、CDC 和行政部门的此类互动的例子包括与拉尔夫上校的会面。 埃里克森，GEIS（国防部全球新发感染系统）主任，参与防御威胁 减少机构分包合同（HDTRA-07-9-0003），并参加联合恐怖主义特别工作组的情况介绍会 特工（联邦调查局/司法部）已就此次事件的影响向白宫提出建议。 NWRCE 主任还参加了向 FBI 提供建议的会议。 与学术机构在核、技术和生物威胁风险方面的关系。 董事们与太平洋西北国家实验室（高院PI）Dick Smith进行了交流 吞吐量蛋白质组学），并将继续探索 PNNL 和 NWRCE 相互作用的方式。 NWRCE 的人员数量，其中最著名的是应急响应主任 Jeff Duchin MD，拥有 CDC Duchin 博士也拥有丰富的经验，并曾多次促进与该机构的沟通。 作为公共卫生部门负责人，在地区公共卫生部门拥有广泛的人脉 健康 - 西雅图和金县。他帮助促进了与该市公共卫生实验室的联系， 此外，NWRCE 还参与了多项拨款申请。 在这两个案例中，NWRCE 都是生物技术公司（Implicit Biosciences 和 Micronics, Inc.）。 由于其精选代理能力和专业知识而受到青睐，这些互动非常富有成效。 随着中心进入新的研究领域、增加新的研究人员和移动，可能会增加 产品投入开发。 NWRCE 将扩大其能力，成为蛋白质组学、基因组学和蛋白质组学国家资源的一部分。 NWRCE 在这些领域创造了研究革兰氏阴性菌感染的生物信息学能力。 方法论并将其应用于革兰氏阴性菌的基础科学、蛋白质组学和基因组方面的研究 这项工作产生了可供生物防御/EID 研究人员使用的信息和数据库， NWRCE 将继续利用其具体重点和重点。 规模经济整合来自整个传染病领域、生物防御网络、 及其自身的研究成果，以提高其作为资源的价值。 并通过国家 RCE 等合作机制提供资金。 此外，还有物质资源。 由 NWRCE 研究生成（仪器、突变体库、化合物筛选和库、 和独特的转基因小鼠品系）将加强和加速中心外的研究。 NWRCE 将与该地区的其他努力以互补的方式发挥作用，以促进 X 区域内的国家生物防御和新发传染病研究工作超过 10 亿。 目前仅 NIAID 就资助了俄勒冈州华盛顿州的 315 项研究经费。 爱达荷州和阿拉斯加州，其中 44 人因 NIAID A 类至 C 类优先病原体的研究而获奖。 传染病研究的资金也通过其他机构（例如 NHLBI、 NIDDK 和 NIGMS 这个科学界联合起来创建了一个具有全国意义的基础设施。 华盛顿大学正在进行的另一个重要的研究工作是细菌感染性疾病。 蒙大拿州落基山实验室正在进行发病机制研究。 与 NIH/NIAID 机构的两位研究人员 Joe Hinnebusch 博士和 Jean Celli 博士合作， 该实验室分别为 V. peso's 和 F. tularensis 提供专业知识和实验模型。 改造完成以创建 BSL-4 实验室；尽管 NWRCE 目前没有研究风险的计划； 第 4 组代理商可以在此类活动中使用这些设施，这种合作提供了极好的机会。 与 RML 的科学家和设施进行合作、协调研究的机会。 革兰氏阴性和革兰氏阳性感染以及媒介传播疾病中的 RML 补充了以下方面的努力 NWRCE 以及机构之间持续的关系将为双方创造利益（见信函） 支持）。 NWRCE 将继续将基本的生物学信息转化为有用的治疗方法和其他方法 NWRCE 的结构是为了将基本发现快速转化为实践。 在第一个资助期内，该中心将两种候选疫苗推进了动物试验，并已完成。 为了响应 NIAID 计划的要求，该应用程序开发了几种领先的抗菌化合物。 重新将产品开发计划的重点转向创建可在广泛范围内发挥作用的疗法 这些项目已经在生物靶标识别、化合物筛选方面做好了准备。 ＆药物化学，以及功效动物模型。 NWRCE 将成为一个重要的资源并维护当前信息的数据库 活跃的细菌病原体，并开始了解病原体的多样性和人类的多样性 21世纪的挑战是了解和整合病原体。 和人类多样性来理解和预测传染病的结果是 NWRCE 的目标 - 并且 奥尔森和米勒博士的部分目的是开始这项努力并发挥领导作用。 是定义囊性纤维化铜绿假单胞菌天然分离株基因型和表型的领导者 Aderem 博士、Martin、Wilson、Hajjar、Ernst、Miller 和 Wurfel 是定义这一概念的领导者之一。 人类对革兰氏阴性菌反应的差异。