Key Findings
About the Co-Author
Rick Cote, Professor of Molecular, Cellular, and Biomedical Sciences
Contact information: Rick.Cote@unh.edu, 603-862-2458, Cote Lab website
This research first published in the Journal of Molecular Biology.
Researchers: R. Gupta, Y. Liu, H. Wang, C. Nordyke, R. Puterbaugh, W. Cui, K. Varga, F. Chu, H. Ke, H. Vashisth, and R. Cote
Revolutionary new findings on the cause of color blindness and certain retinal degenerative diseases that lead to blindness have been published by researchers at the UNH College of Life Sciences and Agriculture. Led by Richa Gupta, a doctoral student at the College, the study provides a deep dive into the structure and function of phosphodiesterase-6 (PDE6) - a protein central to color vision and often linked to retinal degenerative diseases.
The study resulted in the highest resolution crystallized image of PDE6 and the first atomic-level structural model of the enzyme in cones - one of the two photoreceptors found in the eye. These findings give a molecular explanation for why certain PDE6 mutations cause vision problems and could pave the way for treatments that address the root cause of these conditions.
Gupta worked with researchers from the University of North Carolina at Chapel Hill to create an atomic level structure of crystallized PDE6. Independently, she also created high-resolution models of the protein when it was bound to regulatory molecules. Then, she teamed up with Chris Nordyke and Yong Liu, both doctoral students in the College, to analyze the ways PDE6 binds to regulatory molecules and whether these interactions lead to functional changes that impact vision. Nordyke is a biochemistry doctoral student in the lab of Krisztina Varga, associate professor of molecular, cellular and biomedical sciences, and Liu is a chemical engineering doctoral student in the lab of Harish Vashisth, associate professor of chemical engineering.
According to Rick Cote, director of the Center of Integrated Biomedical and Bioengineering Research and Gupta's advisor, "Richa's findings allow us to better interpret the negative effects of inherited mutations on the structure and function of PDE6. This helps us understand how these mutations cause visual dysfunction and disease."
“Richa's findings allow us to better interpret the negative effects of inherited mutations on the structure and function of PDE6. This helps us understand how these mutations cause visual dysfunction and disease.”
The groundbreaking study conducted by the UNH College of Life Sciences and Agriculture provides a clear understanding of how PDE6 is regulated during visual signaling in the retina and could lead to new treatments for these debilitating conditions.
This work is supported by the National Institutes of Health with the goal of developing therapies that will restore and/or prolong normal vision in humans with inherited defects in the PDE6 protein.
