MTM1: Network properties of fungal-bacterial interactions: Predictive modeling and functional analysis of the Hawaiian Drosophila gut microbiome

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How an animal develops, reproduces, and adapts to its environment depends upon not only the traits encoded by its genome, but, as well, the contributions of its microbiome. In many microbial communities, the interactions between bacteria and fungi have profound effects on community properties and host physiology. However, little is known about the mechanisms by which interactions between kingdoms contribute to a healthy microbiome and promote host fitness. This proposal seeks to understand the role of bacterial-fungal interactions in the host physiology of Drosophila (pomace flies) from the Hawaiian clade. Hawaiian flies have adapted to a wide range of environments and lifestyles. The remarkable diversity of Hawaiian Drosophila ecology together with the relatively simple mix of bacterial and fungal species found in their gut provide an excellent system for understanding how microbes help host animals adapt to diverse habitats and diets, potentially catalyzing the evolution of new species. Elucidating the basic principles that govern microbe-microbe and microbe-host interactions holds promise for the development of novel antimicrobial treatments and improving the cultivation of agricultural products. The findings of the proposed project will have broad applicability to the conservation of endangered native Hawaiian fauna (including Drosophila) by identifying microbe-related strategies that will improve host health and survival. The University of Hawai‘i and Chaminade University of Honolulu are minority-servicing institutions with Native Hawaiian students comprising, respectively, 16.5% and 19% of the student body. Involving students from underserved populations with data science and microbiology methods, including the tools developed for this project, will increase the pool of trained scientists in the region and encourage multi-generational Native Hawaiian engagement with STEM.The central hypothesis of this proposal is that bacterial-fungal interactions benefit host fitness by stabilizing the microbiome and enhancing host metabolic processes. Preliminary work using in silico network modeling, high throughput amplicon sequencing data, and microbial manipulation experiments reveal that i) bacterial and fungal members in the gut of Hawaiian flies are likely to interact based on their patterns of co-occurrence; and ii) fungal function is critical for host fitness. The central hypothesis will be addressed with the following approaches: first, computational tools will be generated to allow robust prediction of microbial interactions and emergent community phenotypes such as stability, growth, and resilience to pathogens. Second, bacterial and fungal species will be isolated from native Hawaiian Drosophila guts and cultured in isolation or in pairwise combinations. Metabolomic profiling and measurements of community properties under normal and stressed conditions will be used to identify differences between mixed and pure communities as well as beneficial and deleterious combinations. The data will be used to refine and validate in silico models. Finally, the effect of interkingdom interactions on host physiology will be determined by inoculating Drosophila with various microbial combinations and measuring the impact on host metabolite profile and life history features such as fertility, stress resistance, and lifespan. Metabolomic data will be used to identify candidate pathways underlying microbial-host interactions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.