Brittany Carr

Project Description

Retinal degenerative diseases are genetic disorders of the retina in which patients slowly lose their vision, resulting in blindness. Retinitis pigmentosa is a disorder causing death of rod photoreceptors, while other retinal degenerations affect both rods and cones, or primarily cones. Rods and cones are the light sensitive cells of the retina. They are named for the shapes of their light sensitive outer segment organelles, which are modified non-motile cilia. The outer segments contain a highly organized stack of non-contiguous (rods) or contiguous (cones) disk-shaped membranes that contain very high concentrations of the G-protein coupled receptor rhodopsin. The exact mechanism by which these disks form is unclear. However, it is clear that defects in biosynthesis of both the disks themselves, and disk components such as rhodopsin, are responsible for inherited human retinal disease. Disk biosynthesis is proposed to involve the proteins prcad-21 and prominin-1 which form a complex that may be involved in a step such as disk evagination or sealing. We propose to examine the roles of prcad-21 and prominin-1 in disk formation using X. laevis and D. Rerio (frog and fish) knockout animal models, in combination with our newly developed assays for disk membrane synthesis. We will also use transgenic and knockout X. laevis and novel transgene tools to examine the biosynthesis and quality control of the disk component rhodopsin, including the role rhodopsin codon usage in biosynthesis, the roles of different degradation pathways in rhodopsin quality control, and roles of glycosylation and chromophore binding on regulating pathway use.

Research Interests

Retina
Retinal Degeneration
Pharmacology
Imaging

Research Methodology

CRISPR/Cas9
Xenopus laevis
Imaging: Confocal, Electron Microscopy

Faculty

Faculty of Medicine