Fungi can cause devastating diseases in plants and animals, posing an enormous threat to global food security and human health. In humans, fungal diseases are estimated to kill 1.5 million people every year. In plants, fungal pathogens cause serious diseases on most pre- and post-harvesting crops and causes billions of dollars loss worldwide every year. Despite these threats, current strategies for fighting fungal disease are limited to chemical control. In agriculture, fungicides can leave harmful residues in the environment. Further, fungi have developed resistant strains that can survive nearly all major classes of antifungal drugs and fungicides. In order to protect global food security, human health, and the environment it is critical to develop new technologies for combating fungal disease. Small RNAs are short regulatory molecules that can inhibit the expression of their target genes. This is called RNA interference. Recently, the research team discovered that multiple fungal pathogens can efficiently take up RNAs as a nutrient source from the environment. When fungi absorb RNAs that interfere with the expression of critical fungal proteins, their growth and virulence is severely inhibited. This finding allows them to design specific RNA molecules that can target fungal virulence-related genes to protect crops from fungal infection. These RNA-based antifungals can be sprayed onto plant material where they confer fungal disease protection to the plant, through a process called Spray-Induced Gene Silencing (SIGS). Unlike traditional fungicides, these RNA-based antifungals are safe to ingest and do not leave toxic residues in the soil.
This project aims to establish and depoly RNA-based strategies for plant-pathogen immunity. To do this, the project will first address a significant hurdle limiting robust function: RNA rapidly degrades in the environment, especially in the soil, where many plant fungal pathogens originate. The current project aims to tackle this problem, and to further develop RNA-based antifungal strategies. One goal is to design SIGS RNAs capable of protecting plants from four aggressive pathogens. Concurrently, in order to enhance the stability of SIGS RNAs, the PI will develop several classes of RNA delivery vehicles, made of both organic and inorganic materials. While preliminary data shows that these RNA delivery vehicles can enhance the stability of RNAs on plant material, they are not sufficient in protecting RNA in the soil. In order to develop effective RNA-based antifungals to control soil-borne fungal pathogens, the PI will engineer beneficial soil microbes, specifically one bacterium and one fungus, to continuously produce and secrete antifungal RNAs into the soil. Overall, this project will develop the next generation of RNA-based antifungals to combat plant fungal pathogens, which will directly contribute to securing global food security. Further, once developed in plants, these RNA-based antifungal strategies can be translated into human and animal systems.
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.