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

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.