Equipment and Instrument Infrastructure Improvement for the MMRRC at UC Davis

加州大学戴维斯分校MMRRC设备和仪器基础设施改进

Equipment and Instrument Infrastructure Improvement for the MMRRC at UC Davis ABSTRACT & SCOPE OF WORK The Mutant Mouse Resource and Research Center at the University of California, Davis (MMRRC) 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 support alterations and renovations (A&R) of facilities and/or purchase of instruments and equipment in support of non-AIDS research. This application proposes the purchase and installation of equipment and instrumentation to ensure and increase the quality, rigor, and capability of husbandry, production, and phenotyping of mutant mouse lines maintained and distributed by the MMRRC. Specifically, this application requests funds to improve operations, serviceability, functionality and capability of our MMRRC facilities by 1) replacing broken and irreparable cryorecovery and analytical instrumentation and to enable off-site storage of the MMRRC germplasm cryoarchive, 2) upgrading existing animal transfer stations to substantially improve the quality of specific pathogen-free (SPF) husbandry for MMRRC mouse strains, and 3) obtaining and incorporating specialized instrumentation and equipment to facilitate new and implement improvements in musculoskeletal, pulmonary, and behavioral phenotyping capabilities that add substantively to research integrity, rigor, and reproducibility. Funding of this project will accomplish 5 things. First, it will significantly improve cryorecovery and IVF efficiency, thus accelerating the availability and facilitating the rapid dissemination of mouse lines to requesting investigators. Second, it will expedite quality control analysis of the reproductive biology of MMRRC mouse strains, adding valuable information to users regarding sperm phenotype and ensuring their recovery from the cryoarchive. Third, it will dramatically improve the quality of husbandry and health care for MMRRC mice and provide allergen containment to protect vivarium staff. Fourth, it will enable the validation and depth of phenotyping that can be conducted on all MMRRC mouse strains, thus directly responding to users' requests for more extensive and comprehensive testing and analysis. Fifth, it will improve rigor, reproducibility, and transparency in production and phenotyping activities, further supporting efforts by the MMRRC to achieve approved vendor status by institutions across the country. Together, these upgrades will significantly enhance our ability to meet the increased expectations of MMRRC clientele for fully comprehensively validated mouse models and optimize production and phenotyping services. Further, because these upgrades are MMRRC-project specific, they are beyond the support provided by the UC Davis campus for basic operations and maintenance. The overall outcome of this supplement will be to exert a sustained and powerful influence on operations of the MMRRC by improving and expanding its capability to more expertly maintain, manage, and characterize genetically-modified mouse strains and meet the needs of the national biomedical research community conducting NIH-funded research. By doing so, this supplement will provide a sustained benefit to the overall research community and have a positive impact on NIH-funded research. The parent peer-reviewed NIH funded grant (U42OD012210) has been competitively renewed (as of January 1, 2020) for 5 years. A budget of $478,325 (total costs) requested for the remaining months of the current grant year (until January 31, 2024) is less than half the annual total direct cost budget of the parent grant. The proposed activities all fall within the scope of the parent award, which includes archiving, phenotyping, and distributing investigator-derived and Center-produced mutant mouse lines.