CAREER: Molecular Mechanism of Vision

视觉开始于视网膜对光子的吸收。它被视紫红质吸收，视紫红质是视网膜上的一种色素，由与视蛋白结合的视网膜分子组成，并嵌入在杆状光感受器细胞的膜中。光子触发视网膜分子从11-顺式到全反式的光异构化。与视网膜异构化相关的视蛋白构象变化是细胞最终产生视觉信号的原因。视紫红质已经进化成一个非常可靠的探测器：它可以对100万倍的光强度做出反应。同时，它非常灵敏，甚至可以探测到单个光子。当没有光存在时，这种灵敏度要求非常低的“暗噪声”或异构化率。由于热和光，视网膜可以异构化，并且异构化是相同的。为了获得更好的夜视能力，动物进化出了视紫红质，其在37°C下的黑暗噪音减少到每420年一次热异构化事件。这个项目试图回答一个困扰科学家们几十年的问题：是什么机制使视紫红质在不影响其灵敏度的情况下实现其令人难以置信的低暗噪声？特别是，该项目将测试最近在视紫红质分子中发现的广泛的氢键网络阻止热异构化的假设。几个世纪以来，视觉处理一直吸引着学者，这使得这个项目对科学教育和推广具有吸引力，同时对促进对视觉系统的科学理解也很重要。这项研究是物理和生物科学的交叉，将为从高中到博士后的各级学生和研究人员提供有价值的跨学科培训。通过与耶鲁大学社区办公室和纽约城市大学亨特学院的既定合作，该项目将为大学预科生和大学生提供研究机会，其中许多人在科学领域的代表性不足，接触前沿科学研究的机会有限。此外，实验室成员将参加奇卡诺人和美国原住民科学进步协会的年度会议，以招募目前在该部门代表性不足的美国原住民和西班牙裔研究生。通过研究和教育的整合，该项目将把教学和推广与科学发现相结合，同时鼓励在耶鲁大学的科学项目中纳入代表性不足的群体。本项目由分子与细胞生物科学部的分子系统集群和化学部的生命过程化学共同支持。

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.