Platyhelminth drug targets: Identification, annotation, and validation
Nicolas James Wheeler · 2017
The following dissertation describes work performed to probe the biology of flatworms, with a focus on anthelmintic development and target identification and validation. A wide range of molecular and computational approaches were used to achieve this goal. In particular, I show how free-living planaria can be utilized as a model for its parasitic relatives, for answering biological questions and for anthelmintic screening techniques. Through a variety of approaches, I also contribute to the ongoing study and annotation of a large group of flatworm-specific G protein-coupled receptors, the Platyhelminth-Specific Rhodopsin-Like Orphan Family. This family is specific to the flatworms, is the largest clade of GPCRs and the largest taxonomically-restricted gene family in the entire phylum, and a PROF representative may be preferentially expressed in the neural tissue of planaria. Finally, using the PROF as a case study, I comment on the task of functionally annotating GPCRs from parasitic worms and suggest a more wholistic and rigorous approach. The entirety of this dissertation is then discussed, and the results are reinterpreted through a lens that focuses on anthelmintic discovery and development.