MINNESOTA FUTURES RESEARCH GRANT 2016 Proposal Title: Discovery of new antifungal therapeutics using chemical genomics guided bioprospecting. Principal Investigators: Claudia Schmidt-Dannert, Christine Salomon, Chad Myers, Peter Kennedy Abstract: Life-threatening fungal infections have dramatically increased in recent years. Yet, only three different antifungal drug classes are currently available. Limited treatment options, high mortality rates of fungal infections and wide spread occurrence of multidrug resistant fungal pathogens puts urgency into the development of new drugs. Compared to antibacterial drugs, development of antifungal drugs is challenging as these compounds have to target mechanisms in the eukaryotic fungal cell that are distinct from those in human cells. This project aims at prototyping an innovative antifungal drug discovery pipeline that will use an integrated approach consisting of bioactivity screening, metabolite profiling and next-generation high-throughput chemical genomic profiling to identify high-priority antifungals with novel structures and/or predicted mechanisms of action. We will focus our efforts on extracts from Basidiomycota fungi (aka. mushrooms) as one of the greatest untapped sources for novel pharmaceuticals. We have extensive in-house strain collections of these fungi and their fruiting bodies. Our team combines strengths in computational biology, chemical genomics, drug discovery, biochemistry, synthetic biology, genomics and fungal biology. If successful, we will make unique resource accessible for other drug discovery efforts. Proof-of-concept established in this project will facilitate grant applications targeting major federal initiatives aimed at combating antimicrobial resistances and novel drug developments.