CAREER: Molecular Mechanism of Vision

职业：视觉的分子机制

• 批准号: 0955407
• 负责人: Elsa Chui-Ying Yan
• 金额: $ 93.72万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0955407&HistoricalAwards=false
• 关键词: CAREER; Molecular; Mechanism; Vision

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.

视觉开始于视网膜对光子的吸收。它被视紫红质吸收，视紫红质是视网膜中的一种色素，由与视蛋白结合的视网膜分子组成，并嵌入视杆细胞的膜中。光子触发了视网膜分子从11-顺式到全反式的光异构化。视蛋白的构象变化与视网膜的异构化有关，这是细胞最终产生视觉信号的原因。视紫红质已经发展成为一种非常可靠的探测器：它可以对百万倍范围的光强度做出反应。同时，它非常敏感，甚至可以探测到一个光子。这种灵敏度需要非常低的“暗噪声”或异构化率时，没有光。视黄酸可因热和光而异构化，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下的暗噪声每420年减少一次热异构化事件。该项目旨在回答一个困扰科学家数十年的问题：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的机制是什么？特别是，该项目将测试一个假设，即最近发现的广泛的氢键网络在视紫红质分子防止热异构化。视觉处理已经吸引了几个世纪的学者，使这个项目吸引科学教育和推广，以及重要的是推进视觉系统的科学理解。这项研究是在物理和生物科学的接口，并将提供宝贵的跨学科培训的学生和研究人员在各个层次，从高中到博士后。通过与耶鲁大学社区办公室和纽约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，实验室成员将参加科学促进奇卡诺斯和美洲原住民协会的年度会议，以招募美洲原住民和西班牙裔研究生，他们目前在该部门的代表性不足。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，同时鼓励将代表性不足的群体纳入耶鲁大学的科学计划。该项目由分子和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。