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

项目总结 密苏里大学突变小鼠资源和研究中心的首要目标 MMRRC)的目的是优化和改进小鼠模型，以便使用这些模型的生物医学研究可以继续进行 迅速而有效地。MU-MMRRC还进行与资源有关的研究，通常是合作进行的，以 进一步提炼和培育突变小鼠，充分利用小鼠遗传学和相关微生物群的力量 用于生物医学研究。这项建议加强了MU MMRRC的能力，以进一步确定和 通过对生物材料的表征来完善小鼠模型，并增强我们检查 传染病和肠道微生物群的作用。在不久的将来，该设备将增强我们的 正在进行的和拟议的新冠肺炎研究。作为以前补充资金的一部分，MU-MMRRC已经 成功地将这种小鼠株作为人新冠肺炎的模型，表征了病毒的生长和 小鼠鼻内和气溶胶感染后急性疾病的发生与肠道微生物区系和 先前的感染，重述了人类的疾病。随着SARS-CoV-2新变种从人体样本中出现 K18-hACE2小鼠将在评价免疫的发病机制和逃逸方面发挥关键作用。截至2021年5月， 新冠肺炎在美国的幸存者已近3200万人。作为一种急性局部和系统性的 已知炎症反应会导致感染后的长期疾病，如慢性肺病和 对于神经系统疾病，申请补充资金的设备将使MU-MMRRC有能力 进一步确定和完善小鼠模型，以利于短期和长期的生物医学研究。在……里面 此外，该设备将帮助MU-MMRRC扩大其对其他小鼠模型的表型能力，以符合其 通过检查不同的影响来表征和优化小鼠模型的长期研究目标 微生物区系。目前可用于BSL3和ABSL3实验室的设备在全国范围内有限， 在这场大流行期间，有效地减缓了新冠肺炎的研究。扩建BSL3设备的能力 可用于分析感染样本的资源将使MU-MMRRC继续在 生物医学研究界，推动新冠肺炎发病机制研究。这项提议的目标是 因此，为了提供几个预计不仅对新冠肺炎研究人员有用的关键设备， 也为本地区和全国其他研究人员研究小鼠疾病发病机制提供了灵活性 BSL3型号。由此产生的能力扩展将对研究这些毁灭性的疾病和 在一般的老鼠模型上。至关重要的是，这种设备的用途远远超出了大流行，并特别 选择在本资助周期和未来资助周期内加强父母资助的研究目标。 。

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. .