Antimicrobial resistance is a major healthcare challenge globally. Our approach to solving this global crisis is to hunt for novel natural products from microorganisms as leads for drug discovery. We have the largest European collection of the rare Gibellula fungus, which in the wild grows exclusively by colonizing spiders, killing them, and using the cadavers as hosts. In this project, you will culture Gibellula strains in the laboratory and isolate and purify biologically active natural products from the fungi. We will employ two strategies in parallel: a) Fermentation under varying conditions and addition of small molecule elicitors to induce biosynthetic gene clusters, and b) Whole genome sequencing and expression of biosynthetic gene clusters in heterologous hosts. From these experiments, extracts will be prepared and subjected to bioassay-guided separation with antibacterial, antifungal and antiparasitic assays. Components of interest will be purified, their structures elucidated, and biological activities profiled in detail. The project will provide knowledge and training in the latest methods in natural products chemistry, microbiology, genomics, and antibiotic discovery.
