Tuesday, May 21, 2024
5/21/2024
PROJECT SUMMARY Commensal microbes are indispensable for healthy physiology of their eukaryotic hosts and provide essential functions required for host survival, including nutrition and colonization resistance, and perform accessory functions, including immune system development, vascularization, and contribute to behavior. Composition of the microbiome is shaped by many factors. Some influences are acute, such as diet and infection, which rapidly change the commensal population, but it returns to its pre-challenge composition. On the other hand, the genetics of the host have a constant influence on the microbial composition. While increasing pieces of evidence point to host genetics playing a critical role in shaping the microbiome, how it does so is adversely understudied. To eliminate the influence of environmental factors and study only the role of host genetics in shaping the microbiome, a murine model of legacy-independent host-commensal interactions was developed. This model provided the foundational blueprint establishing that the microbiome is impacted by host mechanisms, but how they are impacted has to be investigated. Herein, we describe how we developing this model to dissect the role of host genetics in specific host- commensal interactions. We have identified that the population of Lactobacillus murinus, a prominent member of the gut microbiome, is directly shaped by host genetics. Through an interdisciplinary approach spanning immunology, microbiology, and genetics, we will determine the mechanism directly influencing the intestinal population of Lactobacilli. The proposed experiments will provide an experimental platform by which any host- commensal relationship driven by host genetics can be identified and the mechanism can be determined. Drs. Golovkina and Chervonsky are ideal sponsor and co-sponsor, respectively, for this project. Not only did they establish the legacy-independent host-commensal model, but they are also experts in the fields of microbiology, immunology, and genetics. Dr. Golovkina is a mouse geneticist who has built her career on using inbred mouse strains to identify genes driving phenotypic differences in host-pathogen interactions and co- established the field of microbiome-virus pathogen interactions. Dr. Chervonsky is a renowned immunologist and expert in host-commensal interactions and the influence of the microbiome on autoimmunity. He is also the co-director of the Gnotobiotic Component of the Host-Microbe Core at the University of Chicago. Their laboratories are uniquely situated to support my efforts to study the gnotobiotic models necessary to delineate host-commensal interactions through rigorous genetic studies. They are dedicated mentors to my academic, scientific career at the bench and beyond. All necessary resources to conduct the proposed experiments are found either in the labs already or on campus at the University of Chicago. In addition to having many resources available for scientific use, the University of Chicago is a fantastic training center for postdoctoral trainees.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
