Periodic Reporting for period 1 - DynAppACry (Understanding signaling in photoreceptors involved in the regulation of bacterial photosynthesis genes using serial crystallography and time-resolved spectroscopy.)
Reporting period: 2020-09-01 to 2022-08-31
Living systems are fundamentally dependent on the ability of proteins to respond to external stimuli. This response is characterized by time dependent changes in structure that occur on multiple time scales, from subpicosecond to seconds. These signal-transduction events are far from being fully understood in all photoreceptor classes. The aim of the project is to measure the real-time structural evolution during photoreceptor-mediated signal transduction, a fundamental cellular process that enables diverse organisms to adapt to changing environmental light conditions and regulate important processes including vision, circadian rhythms and photomovement. Using state-of-the-art time-resolved structural biology techniques, we have monitored the dynamic behaviour of a blue-light photoreceptor. The acquired knowledge may help in the engineering of photoreceptors that will enhance the optogenetics toolbox. It should be mentioned that optogenetics have a great potential in contributing to improved treatments for many diseases (e.g. Alzheimer, Parkinson’s, stroke) and therefore research in that direction may have in the long term a great impact in the society.
We have applied state-of-the-art techniques like time-resolved solution X-ray scattering and time-resolved serial synchrotron crystallography as well as serial femtosecond crystallography and macromolecular crystallography to study the signal transduction pathway in a blue-light photoreceptor. Structural changes upon blue-light illumination of the photoreceptor have been observed both in solution and in crystallo. Part of the findings has been presented in the Biophysical Society meeting (2022) and in the Regional Biophysics Conference (2022). The work will be further disseminated in high-impact Journals and conferences (in 2023).
The current findings extend our understanding on the signal transduction pathway on blue-light photoreceptors and pave the way for the engineering of photoreceptors that will enrich the pool of photoreceptors that could be used for optogenetic applications. They also put forward the positive impact that the advent of powerful X-ray sources is able to bring in our lives as they give us new ways to understand fundamental biological processes (e.g. new ways to scan for potential drugs or understand important biological processes related to health).