Our research interests are mainly related with the structure and function of biological system from molecular level to cellular level. The aim of our group is to combine various structural approaches as well as developing new methodologies to determine the architecture of biological system, in vitro and in vivo, from nano-scale to meso-scale, from static to dynamic. Our core task is conducting cutting-edge scientific research, and fostering high-quality talents. In the next five years, we will focus on (i) in situ structural biology, (ii) time resolution structural dynamics of macromolecules, (iii) 3D architectural biology.
1. In situ structural biology
After rapid development and especially the recent technological breakthroughs, cryo-electron microscopy technology (cryo-EM), such as single particle analysis, has become one of the major tools to study structures of macromolecular complexes, opening a new era of structural biology. In the future the structural study of macromolecular complexes in their intact cellular environment will become the next breakthrough of structural biology, which will be achieved with the further development of cryo-EM technology. However, due to the difficulty of sample preparation, low data integrity and low signal-to-noise ratio, most in situ structures of protein complex only have resolutions worse than 20 angstroms. Our research interest is focused on the development of the complete technique workflow, and improving and optimizing the current techniques, which include cryo-focused ion beam technique, new data collection method and strategy, and new algorithm in image processing and data mining. With these technology advances, we will study the in situ structures and functions of important macromolecular complexes in high resolution.
2. Time resolution structural dynamics of macromolecules
The electron irradiation damage is a major factor to limit the resolution of biological samples in cryo-EM technology. The emerging ultrafast electron microscopy (UEM) provides a new opportunity to solve this problem. The successful combination of UEM and cryo-EM will enable us to yield a new technique cryo-UEM and achieve high resolution imaging without radiation damage. In addition, the pump-probe mode of UEM provides us a unique tool to study the time resolved structural dynamics of macromolecular complexes from pico-second to nano-second. One way of this technique is to perform cryo-UEM in diffraction mode, which is called cryo-UED. Our research interests are focused on developing cryo-UEM and cryo-UED techniques, then exploring the physical mechanism of electron irradiation damage, and studying several important protein complexes to analyze their time-resolved dynamic process.
3. 3D architectural biology
The three-dimensional ultrastructures of biological tissues and organs are related to their functions and their changes reflect different physiological states or potential diseases. Recent technology advances of volume electron microscopy (VEM) along with serial sectioning techniques as well as the fast development of big data technology have allowed us to study the architectures of tissues and organs in 3D space and nano-meter resolution, which is called 3D architectural biology. With our recent developed VEM technique (AutoCUTS-SEM) and more in next step in collaborating with Center for Biological Imaging, Institute of Biophysics, we will focus on image processing algorithm developments including registration, segmentation, annotation and quantification, then studying three dimensional ultrastructures of important tissue model systems and investigating quantitative relations between 3D architectures and diseases.
