Professor,“Thousand Talent Program for Young Outstanding Scientists”
Biological machineries are based on massive dynamic interplays of different biomolecules in the cell. From the biophysical point of view, the essential factors of such interplays include force, energy and kinetics. However, for traditional ensemble experiment to determine the force and kinetics in a biological system is intrinsically difficult as they are either too small or too fast. Optical tweezers (optical trapping) is a newly developed high-resolution technique, which is capable to detect force in a pico-Newton level and displacement in a sub-nanometer scale. More importantly, its temporal resolution can achieve sub-millisecond. By utilizing this special tool and combing with single-molecular biological strategies, we are able to directly monitor the dynamic biological events at a single-molecule level. Specifically, we are interested in understanding the underlined molecular mechanisms on the following important processes:
1) The structural effects of chromatin modification on nucleosomal dynamics, gene regulation.
The information carried in the chromatin structure plays crucial role during evolution and can be inherited. Chromatin research has come to the forefront of the modern epigenetics and is believed to hold the key for many unanswered questions in evolution and human diseases. Chromatin modifications directly alert the interactions between DNA and histone, which play important roles in gene regulation. Using single molecular techniques, we aim to unravel the underlying molecular machinery of gene regulation by directly monitoring the processing events of single enzymes walking along on the nucleosome templates and recording the force and kinetics in a real-time manner.
2) Protein unfolding and protein-DNA interactions.
Force holds everything together. By applying force we are able to unfold a single protein by optical tweezers. Different from the most of biochemical methods, which use denaturants to unfold the proteins, an appropriate force load can unfold and refold the proteins in a real time. The proteins never denature or lose their activities in such experiments. By using single molecular approaches, we focus on several important proteins which related to the cancer and gene transcriptions.
1. Gao Y., Zorman S., Gundersen G., Xi Z., Ma L., Sirinakis G., Rothman J. E., Zhang Y., Single SNARE Complexes Zipper in Three Distinct Stages, Science, 337,1340-1343,2012. (Faculty 1000 recommended paper, Science perspective reviewed paper, Science Signaling Editor’s choice)
2. Sirinakis G., Ren Y., Gao Y., Xi Z., Zhang Y., Combined versatile high-resolution optical tweezers and single-molecule fluorescence microscopy, Rev. Sci. Instrum. 83, 093708, 2012.
3. Zhang Y, Sirinakis G., Gundersen G., Xi Z., Gao Y., “DNA Translocation of atp-Dependent Chromatin Remodelling Factors Revealed by High-Resolution Optical Tweezers” (2012) Methods in Enzymology Vol 513: Nucleosomes, Histones & Chromatin Part B, 1st ed., Oxford uk
4. Xi Z., Gao Y., Sirinakis G., Guo H., Zhang Y., Single-molecule Observation of Helix Staggering, Sliding, and Coiled Coil Misfolding, Proc. Natl. Acad. Sci. USA, 109 (15) 5711-5716, 2012
5. Gao Y., Sirinakis G., Zhang Y., Highly Anisotropic Stability and Folding Kinetics of a Single Coiled Coil Protein under Mechanical Tension. J. Am. Chem. Soc. 133, 12749–12757, 2011.
6. Sirinakis G., Clapierc C.R., Gao Y., Viswanathanc R., Cairnsc B.R., Zhang, Y., The 11 RSC Chromatin Remodeling ATPase can Translocate DNA with High Force and Small Step Size. EMBO J. 30, 2364-2372, 2011.
7. Shang Z., Gao Y., Jia T., Mo Y., Vibrational modes study of thymine on the surface of copper electrode using SERS-measurement and the DFT method. J. Mol. Struct., 930(1-3), 60-64, 2009.
8. Sato A., Gao Y., Kitagawa T. and Mizutani Y., Primary Protein Response after Ligand Photodissociation in Carbonmonoxy Myoglobin. Proc. Natl. Acad. Sci. USA. 104, 9627-9632, 2007.
9. Gao Y., El-Mashtoly S. F., Pal B., Hayashi T., Harada K., Kitagawa T., Pathway of Information Transmission from Heme to Protein upon Ligand Binding/Dissociation in Myoglobin Revealed by UV Resonance Raman Spectroscopy. J. Biol. Chem. 281(34), 24637-24646, 2006.
10. Gao Y., Koyama M, El-Mashtoly S. F., Hayashi T., Harada K., Mizutani Y. and Kitagawa T., Time-resolved Raman Evidence for Energy “Funneling” through Propionate Side Chains in Heme “Cooling” upon Photolysis of Carbonmonoxy Myoglobin. Chem. Phys. Lett. 429(1-3), 239-243, 2006.
Education Background & Academic Experience
2013-present Professor, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2012-2013 Associate Research Scientist, Department of Cell Biology, Yale University, New Haven, CT, USA
2009-2012 Postdoctoral Associate, Department of Cell Biology, Yale University, new Haven, CT, USA
2007-2009 Postdoctoral Associate, Department of Biophysics and Physiology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA
2006-2007 Lecture, Institute of laser Science, South China Normal University, Guangzhou, China
2003-2006 Ph.D in Biophysics, Department of Photo Science, Graduate University for Advanced Studies, Kanagawa, Japan
2000-2003 M.S.in Physics, Physics Department, Henan University, Henan, China
1996-2000 B.S.in Physics, Physics Department, Henan University, Henan, China