Associate Professor
Department of Chemistry
University of Florida
Title: Decoding the chemical signals of the worm
Abstract: Nematodes use small molecules to communicate with other worms and to coordinate their development and behavior. The C. elegans genome encodes a large multi-module hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-1) and a large multi-module nonribosomal peptide synthetase (NRPS-1) that are expressed in two essential neurons in the worm, the canal-associated neurons (CANs). PKS-1 and NRPS-1 are conserved across nematode evolution, with homologs found in most parasitic nematode species. We are characterizing the chemical structures of the natural products that are produced by these enzymatic assembly lines in different nematode species and investigating the biological roles of these natural products. For example, in C. elegans, we have shown that PKS-1 and NRPS-1 produce a family of hybrid polyketide-nonribosomal peptides, the nemamides, which promote starvation survival and recovery from larval arrest. We are using CRISPR-Cas9 to sequentially inactivate enzymatic domains in PKS-1 and NRPS-1 to identify biosynthetic intermediates and map the assembly-line process that leads to the nemamides. In addition, we have identified many genes expressed in the CANs that are required for nemamide biosynthesis, and we are investigating their specific roles in the biosynthetic pathway. Our work reveals how PKS-1 and NRPS-1 can produce multiple natural products and indicates that the CANs are important regulators of diverse biological processes in the worm.
Hosts: Oliver Hobert & Daniel Merritt
