A Washington University Gnotobiotic Research, Education and Transgenic (WU-GREaT) center for modeling genetic and environmental effectors of disease pathogenesis - ABSTRACT:
The impact of the microbiome on multiple facets of human health and physiology has become apparent over
the last two decades. There has been a revolution in thinking about how the microbiome impacts health and
disease states, from Alzheimer’s disease, to obesity, to intestinal bowel disease, to susceptibility to infectious
disease among many others. Due to the complexity of the microbiome, investigation of the microbiota’s effect
on the host, the host’s effect on its resident microbiome, and the microbe’s effect on each other, gnotobiotic
animal models that can be carefully controlled are of critical importance. Using these these models, human
microbiomes can be recapitulated and interfaced with specific genetic modifications of the animal host. We can
move from observational biology into true experimental science where hypotheses can be generated, tested,
and new hypotheses generated and new experiments designed - the cycle how major scientific discoveries
are made and validated.
Washington University School of Medicine has been at the forefront of microbiome research, has a substantial
biomedical research portfolio, including $449M in NIH funding in FY18, and dozens of high-impact researchers
who are moving into microbiome research. We have investigators in neurodegeneration, neurodevelopment,
immunology, infectious disease, metabolism, and gut ecology who are observing the interplay between the
microbiome and physiology and disease states. They require ready access to germ-free mice and gnotobiotic
facilities in order to advance their scientific discoveries. Currently, Washington University lacks a centralized
gnotobiotic facility to enable this research, and this proposal is to construct a 11,137 nasf gnotobiotic and
transgenic center in the middle of campus that will be accessible to all research teams.
Key features of the center are that 1) there will be neighborhoods, where investigators with similar interests
can interact and collaborate 2) access to the facility will be “democratized” so that students, post-docs and
other trainees (the next generation of scientists) can learn the technology first hand, experiment with
advancements in technology, and take the technologies and experience to their next career phase 3) there will
be flexible procedure rooms that can be used for specialized equipment or experimental procedures such as
imaging, surgical suites, or environmental controls, 4) it will be integrated with our gene editing and transgenic
cores to enable rapid creation of new mouse strain in a germ-free environment, 5) there is access to multiple,
modalities to analyze results including single cell sequencing, metabolomics, and imaging, 6) there will be
flexible ABSL neighborhoods to facility infectious disease and immunology research, 7) there is expansion
space nearby for when our science outgrows this facility. Training will be a key aspect of the center, and
collaboration and meeting space is incorporated.
