Photoreceptor Dynamics Over Ten Decades of Time

活着的生物体通过被称为光感受器的蛋白质来感知和响应光线，这种蛋白质控制着细菌和植物向阳光移动等过程，并使人类能够看到东西。光感受器可以被认为是开/关开关，这个项目的目标是准确地确定光如何改变光感受器的形状来打开或关闭开关。所获得的知识将对设计新的光触发开关非常有用，这些开关可以有从微生物、植物到动物(包括人类)的广泛应用。项目人员将接受STEM活动的严格培训，因为该项目使用的实验和计算方法是化学、物理和生物的交叉点。此外，研究生和本科生每年将前往英国的一个设施2-3次，收集数据，并与来自不同学科的科学家互动。STEM培训也扩展到高中生，他们每年夏天都会在PI的实验室里呆上10-12周，由一名客座高中教师共同监督。科学研究正变得越来越多的跨学科，而培训的一个重要成果将是使项目人员能够从事跨学科的研究，从而迎接21世纪的科学挑战。光感受器包含一个嵌入的发色团，该项目的目标是准确地确定从最初的吸收到整个光周期--即数十年--发色团的激发如何与蛋白质动力学结合并影响蛋白质动力学。将研究两组光蛋白：光致变色荧光蛋白，可在亮和暗状态之间可逆切换；光感受器，其激发导致结构变化，最终调节并促进光合作用、视觉转导和昼夜节律等生物过程。在每一种情况下，阐明潜在的操作机制仍然是一个中心挑战，这将推动新型光遗传工具的发展及其在超分辨率显微镜等应用中的部署。该项目的目标将通过理论和实验相结合的方式实现，其中分子动力学模拟将通过用光谱报告探针标记的蛋白质的超快测量来实现，以现场-特定的时间-解析从子PS到ms-S时间域的结构动力学。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Living organisms sense and respond to light using proteins called photoreceptors which control processes such as the movement of bacteria and plants towards sunlight and enable humans to see. Photoreceptors can be thought of as on/off switches, and the goal of this project is to determine precisely how light alters the shape of the photoreceptor to turn the switch on or off. The knowledge that will be gained will be very useful for designing new light-triggered switches that can have wide ranging applications ranging from microbes, plants and animals, including humans. Project personnel will receive rigorous training in STEM activities since the experimental and computational methods used in this project are at the intersection of chemistry, physics and biology. In addition, graduate and undergraduate students will travel to a facility in the UK 2-3 times a year to collect data and interact with scientists from a diverse array of disciplines. Training in STEM also extends to high school students who will spend 10-12 weeks in the PI's lab each summer, jointly supervised by a visiting high school teacher. Scientific research is becoming increasingly more interdisciplinary, and an important outcome of the training will be to enable project personnel to engage in cross-disciplinary research, and thereby meeting the scientific challenges of the 21st century.Photoreceptors contain an embedded chromophore, and the goal of this project is to determine precisely how chromophore excitation couples to and influences protein dynamics, from the initial absorption through the complete photocycle - i.e. over many decades of time. Two groups of photoproteins will be studied: photochromic fluorescent proteins that can be reversibly switched between bright and dark states, and photoreceptors where excitation results in structural changes that ultimately modulate and contribute to biological processes such as photosynthesis, visual transduction and circadian rhythms. In each case, elucidating the underlying mechanism of operation remains a central challenge, which will drive the development of novel optogenetic tools and their deployment in applications such as super-resolution microscopy. The objectives of the project will be met using a combination of theory and experiment in which molecular dynamics simulations will be informed by ultrafast measurements of proteins labeled with spectroscopic reporter probes, to site-specifically time-resolve structural dynamics from the sub-ps to ms-s time domain.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.