RNA binding proteins have the potential to regulate many target transcripts, analogous to transcription factors. However, it remains a key goal to understand how this important class of gene regulatory proteins control vital aspects of development, physiology, and behaviour. In this project, we hope to use C. elegans as a system to identify RNA binding protein genes that may work together to influence post-transcriptional regulation in the nervous system. We are combining reverse genetic approaches (RNA interference and genetic loss of function screens) to identify RNA binding proteins playing critical roles in neurobiology. To achieve this goal, we are employing behavioural screening approaches as well as microscopy of neuronal molecular markers to search for phenotypes. We have also developed higher throughput approaches to generate large combinations of double mutant animals from single mutants, allowing us to study genetic interactions among RNA binding protein genes.
Use of an automated behavioural tracking system to screen for phenotypes in RNA binding protein loss of function mutants. Upper left panel shows a representative worm subjected to high-contrast imaging. Upper right panel shows a magnified version of worm on left. Lower panels show the overall movement after 5 minutes of recording a wild-type animal (left) and a mutant animal (right). Image credit: John Calarco