1) Structures and signaling mechanisms of modular photoreceptors

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A superfamily of bilin-based photoreceptors use covalently-attached linear tetrapyrroles (aka. bilins) as chromophores to perceive light signals from a wide range of the visible spectrum spanning near UV to far-red. Upon absorbing a photon, the bilin chromophore undergoes photo-isomerization, and triggers a sequence of structural events that eventually generate a biological signal via modulation of the enzymatic activity of an effector domain and/or downstream protein-protein interactions. We investigate the structural basis for color perception, signaling dynamics and signal integration in bilin-based modular photoreceptors. We apply dynamic crystallography to capture light-induced structural changes in photo-active crystals and dissect signaling-associated motions via structural meta-analysis. Findings of this research offer a structural framework for development and engineering of bio-inspired modular light actuators with universal adaptability and color versatility that benefit biomedical research and clinical applications. image001

2) Photoreceptors involved in photo-protection

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High-energy UV rays are extremely harmful to living organisms because they cause direct damage to DNA, which leads to cell death and cancerous growth if not repaired. Various photo-protection mechanisms are employed to prevent and/or repair damages from UV irradiation in plants and bacteria. In plants, UV-B photoreceptor UVR8 undergoes UVB-induced dimer dissociation that triggers a host of cellular and organismic responses including light-dependent DNA repair by photolyases. Our collaborative research in this area aims to understand at the molecular level how a UV-B signal is perceived by UVR8 and how UV-damaged DNAs are repaired by photolyases using biochemical and biophysical approaches with an emphasis on dynamic crystallography.

3) Light harvesting and photosynthesis in cyanobacteria

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In oxygenic photosynthetic organisms such as cyanobacteria, light energy is converted to chemical energy via light-driven reactions in photosystems located in thylakoid membranes. Phycobilisomes (PBS) are light-harvesting antenna complexes in cyanobacteria. PBS has a distinctive architecture consisting of rods and a core. Light energy harvested by hundreds of antenna pigments in the rods is funneled to the core via highly efficient radiationless energy transfer, and eventually to a special pair of chlorophylls in photosystem II (PSII) that drives photosynthesis. This research is carried out in a full-fledged collaboration with Zhao group of Huazhong Agricultural University in China. We pursue crystallographic investigations of key components involved in light harvesting, photosynthesis and photo-protection. We aim to understand the structural basis of directional energy transfer and photo-protection mechanisms. Findings are expected to have broad impacts on agricultural and bioenergy research.

4) Development and applications of dynamic crystallography

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Watching a biochemical reaction and/or biological process by dynamic
crystallography would provide unparalleled insights into how proteins work at the
atomic level. Transient intermediate structures are difficult to capture by static crystallography, but they hold the key to mechanistic understanding of protein functions. One of the major hurdles for wider applications of dynamic crystallography is that almost all reactions initiated in crystals are in effect irreversible at room temperature, due to X-ray radiation damage, slow reversion rate and/or lattice disorders induced by large-amplitude structural changes. As a result, many important biological processes are not easily accessible even when a crystal is active. To study these reactions and processes at high resolution, we continue to develop experimental and analytical methods in dynamic crystallography.