Our research focuses on biomolecular mechanisms, particularly membrane receptor complexes and energy-related machinery in biological systems. We visualize these molecular processes using electron cryogenic microscopy (cryo-EM), and the main approaches we use are electron crystallography (two-dimensional (2D) crystal specimens or helical objects), electron tomography, and single-particle cryo-EM. We are also exploring new imaging and sample preparation methods to push the limits of cryo-EM use in biology.
Structural dynamics of AAA+ ATPase
We are interested in molecular mechanism of p97 AAA+ ATPase, particularly how it interacts with its cofactor to perform its function. We are investigating how the key residues influence the p97 conformational landscape and how the cofactor impacts the dynamics. We are tightly collaborating with Dr. Tsui-Fen Chou at Caltech.
Different from p97 ATPase with two tandem AAA+ domains, Rubisco activase (Rca) has only one AAA+ domain, which dynamically forms various oligomers. We are studying how its dynamics influence its interaction with Rubisco enzyme, improving the carbon fixation efficiency in higher plants. We will compare the working modes of the two ATPases and understand the functional dynamics of the AAA+ module in a broader sense.
Waheeda et al. (2023); Zhang et al. (2021); Nandi et al. (2021).
Neurotrophin receptor complex
The pro-domain of the neurotrophin precursor triggers neuronal apoptosis by interacting with p75 neurotrophin receptor and sortilin. We are investigating the formation of the receptor complex. Membrane lipids, especially cholesterol, play a role in activating the subsequent substrate cleavage by 𝛾-secretase. We are performing biochemical characterization and single-particle cryo-EM to investigate the interactions between these biomolecules.
Chan et al.
We are studying molecular complex assemblies that play a key role in bioenergetics. We initially collaborated with Dr. Petra Fromme to study redox modulation of chloroplast ATP synthase. We are currently investigating the photosynthetic supercomplex from C. tepidum, to understand how the GSB uses a highly efficient energy transfer system to survive in an extremely low-light conditions. We are also investigating the spatial relationship between the photosynthetic supercomplex and ATP synthase motor.
Puskar et al. (2022); Yang et al. (2020).
Method development for cryo-EM
We are exploring new methods to improve the data quality for image reconstruction and to measure the physical properties of biomolecules or membranes. We are also developing new methods to minimize the particle adsorption at air-water interface or to facilitate single-particle cryo-EM structure determination.