Functional characterization of an invertebrate thyrotropin-releasing hormone pathway in the regulation of growth

Thyrotropin-releasing hormone (TRH) is at the pinnacle of the Hypothalamic-Pituitary-Thyroid axis responsible for the regulation of diverse physiological and metabolic processes in vertebrate animals. On the other hand, malfunctioning of the TRH regulatory system causes neurological, metabolic, and growth disorders in humans. Recent evidence suggests that components of the TRH signalling axis are evolutionary conserved in invertebrate species, but little is known about the function and mode-of-action of TRH in these species. Recently, our research group identified two TRH-related neuropeptides encoded by a single gene in the genome of the small roundworm Caenorhabditis elegans that are able to bind and activate the C. elegans homolog of the human TRH receptor. This discovery allows the comprehensive characterization of the genetic and functional mechanisms of the invertebrate TRH signalling system in C. elegans. Results from the proposed in silico, biochemical, functional, and omics analyses will clarify the evolutionary origin of the regulatory effects of TRH, and contribute significantly to our mechanistic understanding of the broad physiological functions of this neuropeptide system. Hence, findings from this project are expected to advance our knowledge on the role of TRH in human health and disease.