Hongjie Li, PhDAssistant Professor

Life relies on proteins that convert light into biological signals. From microbial photoreceptors to the human visual system, these proteins initiate diverse biological processes by transforming photon energy into structural changes that ultimately regulate cellular functions. Despite decades of research, a fundamental question remains unanswered: how do atomic-scale structural changes propagate through proteins to generate biological function?

Our laboratory seeks to answer this question by combining structural biology with time-resolved methods. Rather than viewing proteins as static structures, we aim to capture their motions during signal transduction and enzymatic reactions, revealing how biological functions emerge through molecular dynamics across a wide range of timescales.

Our current research focuses on three interconnected areas.

Structural basis of light sensing and signal transduction

We investigate photoreceptor proteins from microorganisms to vertebrates, including microbial rhodopsins, cyanobacteriochromes (CBCRs), and animal visual pigments. Using cryo-electron microscopy and X-ray crystallography, we determine high-resolution structures of different functional states to understand how light absorption triggers conformational changes, color tuning, and downstream signaling.

Time-resolved structural biology

Biological functions are inherently dynamic. We employ X-ray free-electron lasers (XFELs) and time-resolved crystallography to visualize transient intermediate states during photoreception and catalysis. By capturing protein motions from femtoseconds to milliseconds, we aim to construct molecular movies that directly connect structural dynamics with biological function.

Engineering light-responsive proteins

Insights gained from structural studies provide a foundation for engineering photoreceptors with tailored optical and functional properties. We are interested in developing proteins for optogenetics, near-infrared fluorescent imaging, and synthetic light-controlled biological systems.