The long term goals of our research are to identify mechanisms that contribute to the formation and maintenance of photoreceptor outer segments. The goal of this proposal is to explore the regulation of small GTPases that belong to the ARF-like family of proteins and their effect on early development of cilia and photoreceptor outer segment morphogenesis. Interestingly, mutations in small GTPases and their regulators are linked to blindness and syndromic diseases. Our study will also focus on the need for small GTPases in protein trafficking and will test if these GTPases are needed in adult photoreceptors. We will use a combination of unique animal models, cell culture models and in vitro biochemical analyses to comprehensively address the requirement for GTPases and their regulation in ciliated cells including photoreceptors. Our proposed studies are aligned with the Retinal Diseases Program of the NEI to ?Identify the genes involved in both inherited and retinal degenerative diseases (including RP), determine the pathophysiological mechanisms underlying these mutations, and determine new potential therapeutic strategies for treatment such as gene transfer, tissue and cell transplantation, growth factor therapy, and pharmacological intervention?. Our proposed studies have clinical implications, such as therapy for mutations in small GTPases that lead to blindness, and which are not currently available.
This project is aimed at identifying the need for small GTPases in light-sensing photoreceptor cells with the hope of identifying novel therapies for patients with Joubert and/or other syndromic diseases that can cause blindness.
| Moye, Abigail R; Singh, Ratnesh; Kimler, Victoria A et al. (2018) ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure. Mol Biol Cell 29:1590-1598 |
| Wright, Zachary C; Loskutov, Yuriy; Murphy, Daniel et al. (2018) ADP-Ribosylation Factor-Like 2 (ARL2) regulates cilia stability and development of outer segments in rod photoreceptor neurons. Sci Rep 8:16967 |
