Enhancement of existing ABSL3 facilities to accommodate expanded mouse validation and phenotyping

增强现有的 ABSL3 设施以适应扩展的小鼠验证和表型分析

• 批准号: 10406101
• 负责人: KC KENT LLOYD
• 金额: $ 48.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406101
• 关键词: 2019-nCoV; Acute; Address; Administrative Supplement; Aging; Alveolar; Anesthesia procedures; Animals; Autopsy; Blood; Body Weights and Measures; Budgets; COVID-19; California; Cells; Collection; Communicable Diseases; Communities; Complex; Containment; Direct Costs; Disease; Ensure; Environment; Equipment; Funding; Grant; Health; Housing; Infectious Diseases Research; Intestinal Content; Irrigation; Kinetics; Laboratories; Location; Long COVID; Longitudinal Studies; Maintenance; Mus; Mutant Strains Mice; Organ; Parents; Pathologist; Peer Review; Phenotype; Physical Examination; Preparation; Procedures; Pulmonary Pathology; Request for Applications; Research; Research Personnel; Resources; Respiratory System; SARS-CoV-2 variant; Safety; Sampling; Scientist; Surface; Testing; Time; Tissue Banks; Tissue Harvesting; Titrations; U-Series Cooperative Agreements; United States National Institutes of Health; Universities; Validation; Virus; Virus Diseases; Work; aged; cost; equipment acquisition; experimental study; foot; heart function; human disease; instrumentation; mouse model; parent grant; pathogen; prophylactic; pulmonary function; response; whole animal imaging

ABSTRACT & SCOPE OF WORK The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC-UC Davis) is pleased to submit this administrative supplement for up to 1 year of support in response to ORIP’s participation in PA-20-272, “Administrative Supplements to Existing NIH Grants and Cooperative Agreements” specifically related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). This application addresses a number of the stated objectives of the call to support general and biocontainment- related alterations and renovations of existing facilities and to purchase equipment to facilitate COVID-19 and other infectious disease research in small animals. Specifically, this application requests funds to enhance and expand capacity and functionality of our existing ABSL3 vivarium and testing facility by 1) purchasing additional mouse caging and related husbandry equipment to double our ABSL3 biosafety housing, maintenance, and testing capacity for mice, 2) obtaining equipment that facilitates increased mouse handling and testing throughput for infectious disease research requiring ABSL3 containment, and 3) procuring laboratory instrumentation for virus preparation and trituration, and mouse challenge and phenotyping activities dedicated to infectious disease research, including SARS-CoV-2 and COVID-19. Funding of this project will accomplish 3 things. First, it will enable us to conduct additional and more complex mouse-related studies than we can currently perform simultaneously, thus accelerating and extending our abilities to respond to a greater variety of researcher needs and in a more timely manner. Second, it will allow us to conduct long-term studies on mouse models after infectious virus challenge, which will permit and catalyze research on aged mice and the pathophysiological consequences and complications of virus infection on the host, such as post-acute sequellae of COVID-19 (PASC). Third, it will permit efficiencies in virus challenge studies and consolidation of phenotyping activities within the ABSL3 facility, such as measuring body weight kinetics, assessing cardiac and lung function, performing necropsy and harvesting tissues (organs, cells, blood, intestinal contents, etc), and whole animal imaging. Together, these upgrades will significantly enhance our ability to conduct infectious disease research on mouse models that require ABSL3 conditions in support of the scientific community and users of the MMRRC resource. This proposal directly addresses a number of the stated objectives of this special NIH call. The parent peer-reviewed NIH funded grant (U42OD012210) has been competitively renewed (as of January 1, 2020) for 5 years. A budget of $482,305 direct costs ($485,622 total costs) requested for the remaining months of the current grant year (until January 31, 2022) is less than half the annual total direct cost budget of the parent grant. If funded by this supplement, the impact of the proposed experiments will be to add critically important and urgently needed new capabilities and capacities for studies of SARS-CoV-2 and related viruses and treatment and prophylactic strategies relevant to human disease, especially research to investigate and treat the long-term health consequences of COVID-19, and to understand and respond to new SARS- CoV-2 variants.

摘要和工作范围 加利福尼亚大学戴维斯分校（MMRRC-UC Davis）的突变老鼠资源和研究中心 很高兴提交此行政补充剂以响应Orip的最多1年支持 参与PA-20-272，“现有NIH赠款和合作协议的行政补充” 特别与严重的急性呼吸道综合征冠状病毒2（SARS-COV-2）疾病（COVID-19）有关。 该申请介绍了支持一般和生物内在的呼叫的许多既定对象 - 现有设施的相关更改和改革和购买设备以促进Covid-19和 小动物中的其他传染病研究。具体而言，本申请要求资金增强和 通过1）购买额外 鼠标和相关的饲养设备，使我们的ABSL3生物安全外壳，维护和 小鼠的测试能力，2）获得促进鼠标处理和测试增加的设备 需要ABSL3遏制的传染病研究的吞吐量，3）采购实验室 用于病毒制备和三次的仪器，小鼠挑战和表型活动专用 传染病研究，包括SARS-COV-2和COVID-19。该项目的资金将完成 3件事。首先，这将使我们能够进行更多且更复杂的小鼠相关研究 目前同时执行，从而加速并扩展我们对更大种类做出反应的能力 研究人员的需求和更及时的方式。其次，这将使我们能够对 感染性病毒挑战后的小鼠模型，该模型将允许并催化对老年小鼠和 宿主病毒感染的病理生理后果和并发症，例如急性后 COVID-19（PASC）的后遗症。第三，它将允许在病毒挑战研究中效率和合并 ABSL3设施内的表型活动，例如测量体重动力学，评估心脏 和肺功能，进行尸检和收集组织（器官，细胞，血液，肠内容物等）， 和整个动物成像。这些升级在一起将大大增强我们进行感染力的能力 疾病研究需要ABSL3条件以支持科学界和 MMRRC资源的用户。该提案直接解决了此建议的许多既定目标 特殊的NIH电话。由父母同行评审的NIH资助的赠款（U42OD012210）已有竞争性更新 （截至2020年1月1日）持续5年。要求的预算为482,305美元的直接费用（485,622美元的总费用） 当前赠款年度的剩余几个月（直到2022年1月31日）少于年度总成本的一半 父母赠款的预算。如果由此补充资助，则建议的实验的影响是增加 至关重要且迫切需要新的能力和能力，以进行SARS-COV-2和相关的研究 病毒，治疗以及与人类疾病有关的预防策略，特别是研究 并治疗Covid-19的长期健康后果，并理解和回应新的SARS- COV-2变体。