NSF/BIO-UKRI/BBSRC: Tipping the balance of amphibian microbiome-immune interactions towards greater antifungal defences

Infectious fungal diseases are a growing global threat to biodiversity, ecosystem health, and human welfare, with amphibians among the most severely affected animal groups. Because amphibians play critical ecological roles in controlling insect populations, supporting food webs, and serving as indicators of environmental change, their decline can destabilize ecosystems and indirectly impact agriculture, public health, and environmental resilience. A central unresolved question is why some amphibian species can resist fungal infection while others are highly susceptible. This project addresses this problem by studying how the skin microbiome and immune system interact to influence disease outcomes. Using frogs as a model system, this work will investigate how beneficial skin microbes and immune defenses work together to maintain health, how this partnership breaks down during fungal infections, and why resistance varies across species. This project will, thus, advance fundamental understanding of host-microbe interactions. In addition to advancing basic science, the project may inform new strategies to protect wildlife and manage fungal diseases in agricultural and human health settings by integrating microbiome engineering and immune system manipulation to control infectious diseases. The project will also contribute to workforce development by training students and early-career researchers in interdisciplinary approaches spanning immunology, microbiology, and computational biology, and will support broader impacts through engagement with conservation practitioners, museums, and public education initiatives. In addition, this project advances NSF’s priorities in Biotechnology. Invasive fungal diseases are rising globally, threatening biodiversity and human health, with the amphibian pathogen Batrachochytrium dendrobatidis (Bd) causing major population declines. While both host immunity and skin microbiomes influence Bd resistance, how these systems interact remains unclear. This project examines how skin-resident immune cells, antibodies, and microbial communities jointly determine disease outcomes in amphibians. Using Bd-resistant Xenopus laevis and susceptible Atelopus zeteki, we will test the hypothesis that species-specific interactions between skin immunity and microbiomes govern antifungal defense. We will experimentally manipulate microbiomes and immune components to define how these systems influence each other and how Bd disrupts their balance. Integrating immunology, microbiology, and genomics, we will use single-cell RNA sequencing, metagenomics, transcriptomics, flow cytometry, and spatial tissue analyses to map immune-microbiome interactions during infections. Targeted perturbations of mast cells, Langerhans cells, mucosal antibodies, and probiotic bacteria will reveal mechanisms of immune tolerance and pathogen resistance at skin barriers. This collaborative award is made possible through the NSF-UKRI lead agency opportunity. 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. NSF Award ID: 2622393 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Leon Grayfer | Institution: George Washington University, WASHINGTON, DC | Award Amount: $1,199,311 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2622393 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2622393.html