Investigating the role of a novel fungal RNA in intestinal innate immunity and inflammation

The human gut is home to a complex ecosystem of microbes, including fungi. While bacterial contributions to gut health and disease have been extensively studied, the role of the fungal community (mycobiota), remains largely unexplored. Emerging evidence suggests that disruptions in the fungal community (fungal dysbiosis), play a significant role in inflammatory diseases such as inflammatory bowel disease (IBD). Despite this, little is known about how gut fungi interact with the host immune system during health and disease. Our recent research has identified a novel fungal RNA molecule, termed fungal stimulatory RNA (fsRNA), which activates the intestinal immune responses. Unlike other non-stimulatory eukaryotic RNAs, fsRNA triggers immune responses, suggesting an RNA-based communication mechanism between fungi and the host immune system. The goal of this proposal is to investigate the role of fsRNA in modulating intestinal innate immune responses and contributing to inflammation. By using interdisciplinary approaches such as fungal genetic engineering, long- read RNA sequencing, advanced imaging, and in vivo disease models, we aim to uncover the mechanisms of fsRNA-triggered immunity and its impact on gut inflammation. Understanding the interactions between fungal RNA and the immune system could reveal a novel mode of fungal-host communication and highlight new therapeutic targets for treating IBD. This research is expected to expand our knowledge of host-mycobiota interactions by shifting the focus from traditional protein-based virulence factors to RNA-based immune modulation. Ultimately, the findings could lead to innovative therapeutic approaches for managing inflammatory diseases and potentially open up new avenues for the development of RNA-based therapies.