With this award, funded by the Chemistry of Life Processes Program in the Chemistry Division, Dr. Rebecca A. Butcher of the University of Florida is investigating the chemical signals used by different species of nematodes (roundworms) to control their development. Nematodes are very diverse (over 25,000 characterized species) and can be parasitic, causing widespread disease in plants and animals (including humans). Despite the huge impact of nematodes, surprisingly little is known about chemical signaling in members of this important class of organisms. Investigations into the chemical structures and biosynthesis of the chemical signals used by nematodes should enable the development of new chemical tools and strategies to interfere with their life cycles and survival and thus provide new treatment options. This award also promotes the development a discovery-based laboratory course for undergraduates in the isolation of natural products from microorganisms that live inside plants. In this course, students isolate endophytes from plants, generate extracts from these endophytes, and screen the extracts for anti-nematode activities.
This award aims to characterize the chemical structures of key small-molecule signals that nematodes use to control their development. The small-molecule signals from representative nematode species can be identified using comparative metabolomics between wild-type worms and biosynthetic mutants. The relevant compounds are then be purified using mass-guided fractionation, and their structures characterized using NMR spectroscopy. Comparison of the chemical structures and biosynthetic gene sequences from different nematode species enables the roles of specific enzymatic domains to be mapped across nematode evolution. To study the activities of specific enzymatic domains, this study uses a multidisciplinary approach incorporating tools from biochemistry, organic chemistry, structural biology, analytical chemistry, and nematode genetics. The results of this award are expected to shed light on how nematodes control their life cycles and the development of novel methods to reduce the survival of parasitic nematodes. The educational portion of this project increases retention of undergraduate students in science fields by developing a discovery-based (rather than cookbook style) laboratory course in natural product identification. The proposed course extends the research opportunities for undergraduate and high school students and may lead to the discovery of novel bacterial/fungal metabolites with anti-nematode activities.