This project aims to use photoswitchable agonists of the vitamin D receptor (VDR), combined with cutting-edge techniques such as time-resolved protein crystallography and hydrogen-deuterium exchange (HDX) photopharmacology, to establish causal links between time-dependent molecular mechanisms and the transcriptional regulation of genes associated with beneficial and adverse physiological effects of VDR.
This approach will enable precise spatial and temporal control of VDR activity, providing mechanistic insights into how activation dynamics influence gene regulation across different cell types. Ultimately, the project aims to clarify the balance between the beneficial and adverse effects of VDR activation in different tissues and contribute to the development of light-controlled therapies with improved target selectivity and reduced systemic adverse effects.