Research Topics

Structural biology helps us understand how proteins and other biological macromolecules work by revealing their three-dimensional structure at the atomic level. This knowledge is essential for uncovering how biological systems function and for designing more precise medicines. One of the major promises of next-generation X-ray facilities is to move beyond static molecular snapshots toward molecular movies, capturing dynamic processes in real time. Together, structural and time-resolved data provide unique insights into how proteins, the fundamental building blocks of life, function and interact.

The advent of next-generation X-ray facilities, such as the Swiss X-ray Free Electron Laser (SwissFEL) or the upgraded Swiss Light Source (SLS 2.0), open exciting new possibilities for structural biologists. It is now possible to produce high-resolution diffraction patterns from very small crystals while simultaneously outrunning most radiation damage processes. Rapid mixing with substrates or other small molecules allows to follow enzymatic reactions or drug binding in the millisecond range. Time-resolved pump–probe experiments reveal fundamental photochemical reactions like vision or the molecular basis of photopharmacology down to femtosecond timescales.

Naturally light-sensitive retinal-binding proteins are paving the way for time-resolved studies at modern X-ray sources. We have resolved the molecular details of how protons, chloride, and sodium ions are pumped across biological membranes by light. My research further seeks to understand how protein interactions govern the high quantum yield and stereoselectivity of ultrafast retinal isomerization. Our experiments aim to illuminate fundamental biological processes such as the remarkable photo-efficiency of vision and inform the design of improved retinal proteins for optogenetic applications.

Light offers unmatched precision, making it an ideal trigger for time-resolved measurements. Inspired by biology, chemists have developed a diverse repertoire of synthetic photoswitches with highly tunable properties. Like their natural counterpart retinal, these chromophores can be inserted into proteins to place them under optical control. In photopharmacology, reversibly binding ligands are used to precisely control pharmaceutical targets such as ion channels, GPCRs, or microtubules. Compared to optogenetics, this approach offers a broader range of applications—including potential clinical use—because it relies on chemical modification of native proteins rather than genetic engineering. Harnessing the chemistry of synthetic photoswitches to control proteins not natively activated by light will dramatically expand the number of biological systems accessible to time-resolved studies at modern X-ray sources. Dynamic insight into how ligands influence protein conformation will add a crucial new dimension to molecular pharmacology.