CAREER: Molecular Mechanism of Vision

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Vision begins with the absorption of a photon of light by the retina. It is absorbed by rhodopsin, a pigment in the retina, which consists of a retinal molecule bound to the opsin protein and is embedded in the membrane of a rod photoreceptor cell. Photons trigger the photoisomerization of the retinal molecule from the 11-cis to the all-trans form. A conformational change in opsin associated with the isomerization of retinal is what ultimately generates a visual signal by the cell. Rhodopsin has evolved to be a very reliable detector: it can respond to a million-fold range of light intensity. At the same time, it is exquisitely sensitive, detecting even a single photon. This sensitivity requires very low "dark noise" or isomerization rate when no light is present. Retinal can isomerize due to heat as well as light, and the isomerization is identical. To gain ever better night vision, animals evolved rhodopsin whose dark noise at 37°C is reduced to one thermal isomerization event every 420 years. This project seeks to answer a question that has puzzled scientists for decades: What is the mechanism by which rhodopsin achieves its incredibly low dark noise without compromising its sensitivity? In particular, the project will test the hypothesis that a recently discovered extensive hydrogen-bonding network in the rhodopsin molecule prevents thermal isomerization.Visual processing has fascinated scholars for centuries and makes this project appealing for science education and outreach, as well as important for advancing the scientific understanding of the visual system. This research is at the interface of physical and biological science and will provide valuable cross-disciplinary training for students and researchers at all levels, from high school to postdoctoral. Through the established collaborations with the Community Office at Yale and Hunter College of the City University of New York, the project will provide research opportunities to pre-college and college students, many of whom are underrepresented in science and have limited exposure to frontier scientific research. Moreover, the lab members will attend the annual conference for the Society of Advancement of Chicanos and Native Americans in Science to recruit Native American and Hispanic graduate students, who are currently underrepresented in the department. Through the integration of research and education, this project will blend teaching and outreach with scientific discovery while encouraging the inclusion of underrepresented groups in the science program at Yale University.This project is jointly supported by Molecular Systems cluster in the Division of Molecular and Cellular Biosciences and the Chemistry of Life Processes in the Division of Chemistry.