Upgrading infectious disease research facilities at University of Louisville RBL

升级路易斯维尔大学 RBL 传染病研究设施

• 批准号: 10394525
• 负责人: KENNETH E PALMER
• 金额: $ 333.33万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394525
• 关键词: Area; Chills; Collection; Communicable Diseases; Confocal Microscopy; Data; Disease Outbreaks; Emerging Communicable Diseases; Ensure; Equipment; Flow Cytometry; Goals; Image; In Vitro; Infectious Diseases Research; Kentucky; Laboratories; Laboratory Animal Production and Facilities; Laboratory Research; Lighting; Link; Medicine; Metabolic; Modernization; National Institute of Allergy and Infectious Disease; Normal Cell; Normal tissue morphology; Physiological; Plethysmography; Process; Research; Research Infrastructure; Research Personnel; Research Subjects; Resolution; Seasons; Secure; System; Telemetry; Therapeutic; Treatment Efficacy; Universities; Water; biodefense; biothreat; data acquisition; data complexity; improved; in vivo; infectious disease model; instrument; instrumentation; mouse model; operation; prevent; repaired; research facility; response; vaccine discovery

The University of Louisville Regional Biocontainment Laboratory (RBL) is an operational unit of the University’s Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM). The CPM operates the only Biosafety Level 3 laboratories and animal research facilities available to researchers in the Commonwealth of Kentucky. As such we are a regional resource for two Carnegie Research I (highly research intensive) Universities—the University of Louisville and the University of Kentucky—as well as for the local biotechnology industry and other universities and non-profit organizations. The University of Louisville has been an outstanding steward of the RBL, paying meticulous attention to the facility needs. However, after a decade, we have encountered some challenges, primarily with obsolescence of control systems, and wear and tear on some of the building air handling systems. The necessary HVAC upgrades are already being addressed by the University, but we request support from NIAID through this G20 for additional facility related upgrades and modernization of research equipment SPECIFIC AIMS We propose to address specific facility operational needs in both the fixed building infrastructure and in upgrading and modernizing our in vivo and in vitro research capabilities. We propose incorporating modern state-of-the-art instrumentation to build solid foundations for innovations in biodefense and emerging infectious disease research. The building systems upgrades that directly affect operations of the containment space will be scheduled during the annual preventative maintenance shutdown periods to be conducted in November/December 2021 and 2022. Similarly, new in vivo and in vitro research equipment shall be installed during the annual shutdown to allow for service professionals to install and commission the equipment without needing to address biosafety training and Select Agent-specific standard operating procedures. Aim 1: Repair, renovate and modernize RBL building systems to enhance functions and operations of the existing research facilities. We propose to address specific facility operational needs in the fixed building infrastructure. We shall upgrade critical facility systems that are facing imminent obsolescence and rectify one major facility design defect that placed some inconveniences and limitations on research operations: the BSL-3- ABSL-3 passthrough boxes. The long-term commitment of the CPM is to support basic and translational research that leads to the development of countermeasures for biodefense and emerging infectious agents. These upgrades will secure our ability to maintain our BSL-3 research program and continue to develop innovative countermeasures against biodefense and emerging infectious disease threats. Aim 2: Enhance and modernize the CPM RBL in vivo research capabilities. The COVID-19 pandemic validated the significance and need for ABSL-3 facilities such as we have at the CPM. Over the past 14 months our in vivo research facilities were heavily utilized to support development of novel COVID-19 therapeutics, vaccines and other prophylactic strategies. Until COVID-19 the vast majority of our in vivo research utilized murine models, with sporadic use of ferrets for influenza studies. Recently, we have made extensive use of the Golden Syrian Hamster (GSH) model. Consequently, we have a practical need to expand our caging for medium sized rodent models. Moreover, emerging data on post-COVID human pathologies impacting different organ systems—lung, cardiovascular, neural and renal in particular—raise the need for more sophisticated tools for assessing physiological function in research models. To this end, we propose to elevate our in vivo research facilities by adding Promethion metabolic isocaging systems that record animal metabolic and behavioral data and allow us to integrate research studies with our existing gnotobiotic rodent core. We shall also add telemetry capabilities to precisely record body temperature, heart rate and blood pressure metrics. For lung function assessments, we will add rodent plethysmography capabilities. These research infrastructure enhancements will build new collaborations with our colleagues in centers of excellence in environmental health, cardiovascular disease, diabetes and obesity. We will also consolidate existing collaborations with our Functional Microbiomics, Inflammation and Pathogenicity COBRE by facilitating use of gnotobiotic animals to assess the impact of microbiome communities in pathogenesis of emerging infectious diseases. In vivo imaging capability is an extremely useful adjunct to physiological and most-mortem pathology assessments. Our existing IVIS optical imaging system is nearing obsolescence, and needs upgrading to secure ongoing research studies, particularly in Yersinia pestis and Burkholderia pseudomallei infection models. Aim 3: Enhance and modernize the CPM RBL in vitro research capabilities. The CPM RBL is a wellequipped facility, but the vast majority of the research instrumentation was installed as the University cost-share contribution to the RBL construction between 2007 and 2010. We have a meticulous equipment maintenance and service program coordinated by Marlene Steffen and funded by the Executive Vice President for Research annual budget to the CPM, which has kept all of our equipment fit for purpose. Over the past decade, technology Contact PD/PI: PALMER, KENNETH E Program Narrative Page 7 for analysis of immune cell function by flow cytometry has become significantly more sophisticated. We propose to enhance and modernize our flow cytometry analytical capabilities by adding a Becton Dickinson FACSymphony analyzer with 4 laser/16 color capabilities and high throughput system that will accommodate 96/384-well plates. This will significantly expand the speed, throughput and sophistication of the data acquisition, complementing our existing 11-year-old FACSAria II cell sorter. We have existing high throughput screening capabilities in our High Throughput Biology Core. Most of the HTPB equipment is also a decade old. We propose that our biodefense and emerging infectious disease research programs would benefit immensely by acquisition of the Cytation C10 high throughput confocal microscopy instrument that allows rapid collection of high quality and high-resolution quantitative data under normal cell and tissue incubation conditions. Several of our faculty have critical need for this instrument to be located in our RBL BSL-3 laboratories to facilitate their research on emerging viruses and bacterial pathogens.

路易斯维尔大学区域生物内在实验室（RBL）是该大学的运营部门 生物反应和新兴传染病（CPM）的预测医学中心。 CPM操作员 唯一可用于研究人员的生物安全3级实验室和动物研究设施 肯塔基州的联邦。因此，我们是两项卡内基研究的区域资源（高度研究） 强化）大学 - 路易斯维尔大学和肯塔基大学 - 以及当地 生物技术行业以及其他大学和非营利组织。路易斯维尔大学一直 RBL的出色管家，对设施的需求非常关注。但是，十年后， 我们遇到了一些挑战，主要是在控制系统的过时，然后磨损 一些建筑空气处理系统。必要的HVAC升级已经由 大学，但我们要求NIAID通过此G20提供有关其他设施相关的升级和 研究设备的现代化 具体目标 我们建议解决固定建筑基础架构和升级的特定设施运营需求 并使我们的体内和体外研究能力现代化。我们提出结合现代最先进的 仪器以建立生物化和新兴感染创新的固体基础 研究。建筑系统升级直接影响遏制空间的操作的升级将是 计划在年度预防性维护关闭期间进行 2021年11月/12月和2022年。同样，应安装新的体内和体外研究设备 在年度关闭期间，以允许服务专业人员安装和委托设备而无需 需要解决生物安全培训和特定于特定代理的标准操作程序。 目标1：维修，翻新和现代化RBL建筑系统，以增强功能和操作 现有的研究设施。我们建议解决固定建筑中特定的设施运营需求 基础设施。我们将升级面临灭绝的关键设施系统，并纠正一个 对研究操作的一些影响和局限性的主要设施设计缺陷：BSL-3-- Absl-3传送盒。 CPM的长期承诺是支持基本和翻译 导致开发生物化和新兴传染剂的对策的研究。 这些升级将确保我们维护BSL-3研究计划的能力，并继续开发 针对生物化和新兴感染威胁的创新对策。 目标2：增强和现代化体内研究功能的CPM RBL。 19009年大流行 验证了我们在CPM等ABSL-3设施的重要性和需求。在过去的14个月中 我们的体内研究设施大量用于支持新型Covid-19疗法的发展， 疫苗和其他预防策略。直到Covid-19-19-我们绝大多数我们的体内研究都利用 鼠模型，零星使用雪貂进行影响力研究。最近，我们广泛使用了 黄金叙利亚仓鼠（GSH）模型。因此，我们有实际的需要扩大笼子的笼子 大小的啮齿动物模型。此外，关于影响不同器官的杂化后人类病理的新兴数据 系统 - 肺，心血管，神经和肾脏，尤其是 - 使需要更复杂的工具的需求 评估研究模型中的身体机能。为此，我们建议提升我们的体内研究 通过添加promethion代谢异构系统来记录动物代谢和行为数据的设施 并允许我们将研究与现有的gnotobiotic啮齿动物核心结合起来。我们还将添加遥测 精确记录体温，心率和血压指标的能力。用于肺功能 评估，我们将添加啮齿动物的整数功能。这些研究基础设施的增强将 与我们的同事在环境健康卓越，心血管中建立新的合作 疾病，糖尿病和肥胖症。我们还将合并现有的合作与我们的功能微生物学， 通过支持使用gnotobirotic动物来评估的炎症和致病性鞋底 新兴传染病的发病机理中的微生物组群落。体内成像能力是 对物理和大多数病理评估的非常有用的辅助。我们现有的IVIS光学 成像系统几乎是过时的，需要升级以确保正在进行的研究，特别是 在耶尔森氏菌和Burkholderia假单胞菌感染模型中。 目标3：在体外研究功能中增强和现代化CPM RBL。 CPM RBL是设备齐全的设施，但绝大多数研究工具是作为大学成本份额安装的 2007年至2010年之间对RBL构建的贡献。我们有一丝不高的设备维护 由Marlene Steffen协调的服务计划，并由执行副总裁研究 CPM的年度预算使我们所有的设备适合目的。在过去的十年中，技术 联系PD/PI：Palmer，Kenneth E 计划叙述第7页 为了分析流式细胞术对免疫细胞功能的分析，已经变得更加复杂。我们建议 通过添加Becton Dickinson来增强和现代化我们的流式细胞仪分析能力 Facsymphony Analyzer具有4个激光/16颜色功能和高吞吐量系统，可容纳 96/384孔板。这将大大扩大数据采集的速度，吞吐量和复杂的速度， 补充我们现有的11岁的Facsaria II细胞分系程序。我们现有高通量筛选 我们高通量生物学核心的能力。大多数HTPB设备也是十年的历史。我们建议 我们的生物化和新兴的传染病研究计划将通过获取极大地受益 Cytation C10高吞吐量共聚焦显微镜仪器，该仪器允许快速收集高质量 以及在正常细胞和组织孵育条件下的高分辨率定量数据。我们的几个教师 迫切需要该工具位于我们的RBL BSL-3实验室中，以促进他们的研究 新兴病毒和细菌病原体。