Gadusol: An ancient sunscreen that protects metazoan development

Project Summary Sunlight, while essential for life on earth, also produces harmful ultraviolet radiation (UVR) that penetrates the ozone layer. UVR, particularly UVB, is known to damage organelles and DNA. A variety of UVR-protective mechanisms have arisen during metazoan evolution. Until recently, melanin was believed to be the only vertebrate sunscreen. Recently, our lab discovered a novel vertebrate sunscreen named gadusol. Gadusol is maternally deposited from the ovary to the egg to protect against UV damage during the earliest stages of development, prior to the production of melanin. We do not yet know the function of zygotically produced gadusol, after maternally provided gadusol is depleted and fish have developed other UV protective mechanisms including melanin, skin, and scales. Here, I will investigate both the zygotic function and evolutionary origins of gadusol. First, I will determine if zygotically produced gadusol acts as a spatially organized sunscreen and characterize the response to UVR exposure in mutants lacking gadusol and wildtype controls with single cell RNA sequencing. Second, I will determine if UVR exposure upregulates gadusol production as a form of protection against future exposures and the mechanism by which this occurs. Third, I will investigate the evolutionary origins of gadusol, identifying the source and conservation of the gadusol producing enzymes, eevs and MT-Ox, from algal to metazoan species and identify extant species in which eevs and MT-Ox are co-expressed with the melanophore master regulator mitf. This project will provide insights into how this novel vertebrate sunscreen, gadusol, is synthesized and used in vertebrates. My research project will leverage the strong community of zebrafish researchers, developmental biologists, and evolutionary geneticists at the University of Utah to learn techniques and develop skills I will take with me to my own independent research lab.