We are currently pursuing research projects in the following directions.
1) Structures, dynamics and mechanisms of modular photoreceptors
From photosynthesis to human vision, we investigate how photoreceptors perceive a light signal and generate a biological response at the molecular level. We capture local and global light-induced structural events at the atomic resolution using crystallography and cryoEM. Findings will advance the mechanistic understanding of light signaling and allosteric regulation in photoreceptors.
2) Structures and mechanisms of novel bilin lyases
We study a family of newly discovered enzymes responsible for the biogenesis and diversity of light harvesting proteins in photosynthetic organisms. We use X-ray crystallography, bioinformatics and mutagenesis to explore the molecular basis and reaction mechanisms of these bilin lyases that enable extensive pigment diversity in marine Synechococcus for efficient light harvesting. Mechanistic studies on one of the most important post-translational modification reactions in cyanobacteria will lead to the repertoire expansion of biosynthetic enzymes, which produce fluorescent labels of high quantum yield and excellent stability for both biomedical research and therapeutics.
3) Molecular mechanisms of DNA processing enzymes
Using crystallography and cryoEM, we investigate how DNA processing enzymes including DNA polymerases and DNA repair enzymes respond to changes in light and/or redox conditions. Recent discoveries of iron-sulfur cluster [4Fe4S] in eukaryotic DNA polymerases suggest that [4Fe4S] plays an important yet elusive role in DNA replication and DNA repair. Findings from our model systems will inform how living organisms regulate light responses and maintain genome stability at the molecular level.
4) In situ serial diffraction at room temperature
For decades, protein crystallography has been largely limited to non-physiological cryogenic temperatures, which inevitably hinder large protein motions and impede dynamic studies. To address this challenge, we are developing a technology platform that enables high throughput in situ serial diffraction experiments at room temperature. Based on the "crystal-on-crystal" invention, this technology aims to transform crystallography from a static technique to a powerful, widely applicable dynamic method.