Molecular and Circuit Analyses of Color Discrimination without Opsins - PROJECT SUMMARY Light is a critical environmental cue that shapes daily health behaviors such as navigation, foraging, and sleep regulation across the animal kingdom. In humans, disruptions in light-sensing pathways can result in blindness, circadian dysfunction, and other health issues. Studying neurobiological mechanisms underlying light-sensing systems can improve our knowledge of both human health issues and fundamental principles of sensorimotor processing. The proposed research aims to elucidate how the relatively simple nervous system of the nematode roundworm Caenorhabditis elegans processes the color of environmental light to drive changes in foraging behavior. Notably, C. elegans lacks eyes and conventional molecular photoreceptors known as opsins but can discriminate colors of environmental light. The proposed studies seek to exploit the genetic tractability and experimental accessibility of C. elegans to analyze molecular and circuit mechanisms underlying color discrimination by an opsin-less animal and thereby yield generalizable insight into light-sensing systems and sensorimotor processing. Leveraging advanced molecular genetic, neurobiological, and behavioral approaches, the proposed studies will: (1) analyze the wavelength dependance of C. elegans color-sensitive behaviors; (2) define molecular substrates and cellular site-of-action for light processing by non-canonical phototransducers in C. elegans; and (3) identify and functionally analyze how integration across C. elegans photosensory circuits might drive color- sensitive behaviors. Taken together, these experiments will provide insight into how non-canonical phototransducers and integration across sensory circuits enable light responsivity in the absence of opsins. More generally, the proposed studies should increase understanding of elucidating the principles of light sensing and sensory integration systems of significant biomedical and fundamental biological import. In addition, the proposed studies are ideally suited to prepare the PI for an independent faculty position by equipping her with the advanced technical skills and scientific foundation required to pursue research in line with her interests. More specifically, the PI’s long-term goal is to establish an independent research program focused on uncovering how information is represented and communicated within and across neural circuits using C. elegans as a model system. Support from this fellowship – and pursuing these studies in the ideal training environment provided by the Ghosh Laboratory and Dartmouth more generally – will enable her to develop advanced technical expertise in C. elegans genetics and neuroimaging and to characterize a novel sensory integration circuit in C. elegans that will serve as the foundation for lines of inquiry pursued by her laboratory.
