Equipment to facilitate expansion of MMRRC services related to gut microbiota and infectious diseases including SARS-CoV-2 and future infectious agents

PROJECT SUMMARY An overarching goal of the Mutant Mouse Resource and Research Center at the University of Missouri (MU- MMRRC) is to optimize and refine mouse models so that biomedical research using these models can proceed rapidly and effectively. The MU-MMRRC also conducts resource-related research, often collaboratively, to further refine and develop mutant mice and capitalize on the power of mouse genetics and associated microbiota for biomedical research. This proposal enhances the capacity of the MU MMRRC to further characterize and refine mouse models through characterization of biological material and enhance our capability to examine the role of infectious disease and the gut microbiome. In the immediate future this equipment will enhance our ongoing and proposed studies of COVID-19. As part of previous supplemental funding, the MU-MMRRC has succeeded in advancing this mouse strain as a model for human COVID-19, characterizing viral growth and the development of acute disease following intranasal and aerosol infection of mice with variations in gut microbiota and prior infection, recapitulating the disease in humans. As new variants of SARS-CoV-2 emerge from human samples the K18-hACE2 mouse will play a key role in evaluating pathogenesis and escape of immunity. As of May of 2021, there have been nearly 32 million survivors of COVID-19 in the United States. As an acute local and systemic inflammatory response is known to cause long-term post-infectious diseases such as chronic pulmonary and neurological diseases, the equipment requested for supplement funding will permit the MU-MMRRC an ability to further characterize and refine the mouse model for the benefit of short- and long-term biomedical research. In addition, this equipment will help the MU-MMRRC expand its ability to phenotype other mouse models in line with its long-term research goals of characterizing and optimizing mouse models by examining the effects of differing microbiota. Current equipment available for use in the BSL3 and ABSL3 laboratories is limited across the nation, effectively slowing COVID-19 research during this pandemic. Expanding the capacity of the BSL3 equipment resources available to analyze infected samples will allow the MU-MMRRC to continue to play a critical role in the biomedical research community and promote studies of pathogenesis for COVID-19. The objective of this proposal is therefore to provide several key pieces of equipment that are expected to be of use not only to COVID-19 researchers, but also provide flexibility to other researchers in the region and nation for studying disease pathogenesis in mouse BSL3 models. The resulting expansion of capabilities will be critical to research on these devastating diseases and on mouse models in general. Crucially, this equipment has use far beyond the pandemic and has been specifically chosen to enhance the parent grant's research goals during this funding cycle and into future funding cycles. .