Photoreceptor Dynamics Over Ten Decades of Time

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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.