Professor, Department of Physics, National University of Singapore.
DNA mechanics; Single molecular manipulation and imaging
Our research is based on highly sensitive single-molecule manipulation and imaging techniques. It also requires understanding mechanics of biopolymers. Our main research focuses are: Genome compaction and gene regulation in eukaryotic cells, bacteria, and viruses; Virus replication in host cells; Single-molecule detection of specific interactions between DNA and important proteins or enzymes; Micromechanics of biopolymers; Development of novel single-molecule manipulation and imaging techniques.
While being trained in theoretical physics, Dr Jie Yan built a strong interest in studying molecular cell biology using a combination of novel single-molecule biophysical methods and theoretical modeling. Since he joined the Department of Physics of NUS in 2005, he has been leading a group to study DNA-protein interactions and micromechanics of biopolymers. He became a Principal Investigator in MBI in 2009, which he will focus on studies of genome packaging in cells, gene regulation in bacteria, and mechanical responses of mechanosensing proteins to external forces.
SELECTED PUBLICATIONS BY RESEARCH AREAS
- DNA structures and mechanics
- Protein filaments based gene-silencing and regulations
- Mechanisms of mechanosensing proteins
- DNA damage repair proteins
DNA structures and mechanics
Cong, P., Dai, L., Chen, H., van der Maarel, J.R.C., Doyle, P.S., and Yan, J. (2015). Revisiting the Anomalous Bending Elasticity of Sharply Bent DNA. Biophysical Journal. 109:2338-51.
You, H., Wu, J., Shao, F., Yan, J. (2015). Stability and Kinetics of c-MYC Promoter G-Quadruplexes Studied by Single-Molecule Manipulation. Journal of the American Chemical Society (Communication). 137: 2424–2427.
You, H., Zeng, X., Xu, Y., Lim, C.J., Efremov, A.K., Phan, A.T., Yan, J. (2014). Dynamics and stability of polymorphic human telomeric G-quadruplex under tension. Nucleic Acids Research. 42: 8789-8795.
Zhang, X., Qu, Y., Chen, H., Rouzina, I., Zhang, S., Doyle, P., Yan, J. (2014). Interconversion between three overstretched DNA structures. Journal of the American Chemical Society, 136: 16073 -16080.
Zhang, X., Chen, H., Le, S., Rouzina, I., Doyle, P., Yan, J. (2013). Revealing the Competition between Peeled-ssDNA, Melting Bubbles and S-DNA during DNA Overstretching by Single-Molecule Calorimetry. PNAS110: 3859-3864.
Zhang, X., Fu, H., Chen, H., Doyle, P., Yan, J. (2012).Two distinct overstretched DNA structures revealed by single-molecule thermodynamics measurements. PNAS109: 8103-8108.
Fu, H., Chen, H., Zhang, X., Qu, Y., Marko, J.F., Yan, J. (2011). Transition dynamics and selection of the distinct S-DNA and strand unpeeling modes of double helix overstretching. Nucleic Acids Research 39:3473-3481.
Fu, H., Chen, H., Marko, J.F., Yan, J. (2010). Two distinct overstretched DNA states. Nucleic Acid Research 38: 5594-5600.
Protein filaments based gene-silencing and regulations
Desai, S.K., Winardhi, R.S., Periasamy, S., Dykas, M.M., Yan, J. and Kenney, L.J. (2016). The horizontally-acquired response regulator SsrB drives a Salmonella lifestyle switch by relieving biofilm silencing. elife, 5: 10747.
Lee, S.Y., Lim, C.J., Dröge, P., Yan, J. (2015). Regulation of Bacterial DNA Packaging in Early Stationary Phase by Competitive DNA Binding of Dps and IHF. Scientific Reports, 5: 18146.
Winardhi, R.S., Yan, J., Kenney, L. J. (2015). H-NS Regulates Gene Expression and Compacts the Nucleoid: Insights from Single-Molecule Experiments. Biophysical Journal, 109: 1321-1329.
Efremov, A.K., Qu, Y., Maruyama, H., Lim, C. J, Takeyasu, K., and Yan, J. (2015). Transcriptional repressor TrmBL2 from Thermococcus kodakarensis forms filamentous nucleoprotein structures and competes with histones for DNA binding in a salt- and DNA supercoiling-dependent manner. J. Biol. Chem., 290: 15770-15784.
Winardhi, R.S., Gulvady, R., Mellies, J. L., Yan, J. (2014). Locus of Enterocyte Effacement-Encoded Regulator (Ler) of pathogenic Escherichia coli Competes Off Nucleoid Structuring Protein H-NS through Non-Cooperative DNA Binding. J. Biol. Chem. 89: 13739-13750.
Lim, C.J., Kenney, L.J., and Yan, J. (2014). Single-molecule studies on the mechanical interplay between DNA supercoiling and H-NS DNA architectural properties. Nucleic Acids Research, 42: 8369-8378.
Qu, Y., Lim, C.J., Whang, Y.R., Liu,J., Yan, J. (2013). Mechanism of DNA Organization by Mycobacterium tuberculosis Protein Lsr2. Nucleic Acids Research. 41(10):5263-5272.
Lim, C.J., Lee, S.Y., Teramoto, J., Ishihama, A., and Yan, J. (2013). The nucleoid-associated protein Dan organizes chromosomal DNA through rigid nucleoprotein filament formation in E. coli during anoxia. Nucleic Acids Research. 41(2):746-753.
Lim, C.J., Lee, S.Y., Kenney, L.J., Yan, J. (2012). Nucleoprotein filament formation is the structural basis for H-NS gene silencing. Scientific Reports. 2:509.
Winardhi, R.S., Fu, W., Castang, S., Li, Y., Dove, S.L., Yan, J. (2012). Higher order oligomerization is required for H-NS family member MvaT to form gene-silencing nucleoprotein filaments. Nucleic Acids Research. 40:8942-8952.
Lim, C.J., Whang, Y., Kenney, L.J., Yan, J. (2012). Gene silencing H-NS paralogue StpA forms a rigid protein filament along DNA that blocks DNA accessibility. Nucleic Acids Research 40:3316-3328.
Liu, Y., Chen, H., Kenney, L.J., Yan, J. (2010). A divalent switch drives H-NS/DNA-binding conformations between stiffening and bridging modes. Genes & Development 24:339-344.
Mechanisms of mechanosensing proteins
Yao, M., Goult, B.T., Klapholz, B., Hu, X., Toseland, C.P., Guo, Y., Cong, P., Sheetz, M., and Yan, J. (2016). The mechanical response of talin. Nature Communications, 7: 11966.
Le, S., Liu, R., Lim, C. T., Yan, J. (2016). Uncovering mechanosensing mechanisms at the single protein level using magnetic tweezers. Methods, 94:13-18.
Ladoux, B., Nelson, W. J., Yan, J., and Mège, R.M. (2015). The minimal mechanosensing machinery at work at cell-cell contacts. Integrative Biology, 7: 1109-1119.
Yao, M., Chen, H., and Yan, J. (2015). Thermodynamics of force-dependent folding and unfolding of small protein and nucleic acids structures. Integrative Biology. 7: 1154-1160.
Chen, H., Yuan, G., Winardhi, R.S., Yao, M., Popa, I., Fernandez, J.M., Yan, J. (2015). Dynamics of equilibrium folding and unfolding transitions of titin immunoglobulin domain under constant forces. Journal of the American Chemical Society. 137: pp 3540–3546.
Yao, M., Qiu, W., Liu, R., Efremov, A. K., Cong, P., Seddiki, R., Payre, M., Lim, C. T., Ladoux, B., Mège, R. M., Yan, J. (2014). Force-dependent conformational switch of a-catenin controls vinculin binding. Nature Communication. 5: 4525.
Yao, M., Goult, B.T., Cong, P., Sheetz, M.P., Yan, J. (2014). Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Scientific Reports. 4: 4610.
Chen, H., Chandrasekar, S., Sheetz, M. P., Stossel, T. P., Nakamura, F., Yan, J. (2013). Mechanical perturbation of filamin A immunoglobulin repeats 20-21 reveals potential non-equilibrium mechanochemical partner binding function. Scientific Reports. 3:1642.
Chen, H., Zhu, X., Cong, P., Sheetz, M.P., Nakamura, F., Yan, J. (2011). Differential Mechanical Stability of Filamin A Rod Segments. Biophysical Journal 101:1231-1237.
Chen, H, H.X. Fu, X.Y. Zhu, P.W. Cong, F. Nakamura, and J. Yan (2011). Improved High Force Magnetic Tweezers for Stretching and Refolding of Proteins and Short DNA. Biophysical Journal. 100: 517-523.
DNA damage repair proteins
Le, S., Yao, M., Chen, J., Efremov, A.K., Azimi, S., and Yan, J. (2014). Disturbance-free rapid solution exchange for magnetic tweezers single-molecule studies. Nucleic Acids Research. 43: e113.
Chen, J., Le, S., Basu, A., Chazin, W. J., and Yan, J. (2015). Mechanochemical regulations of RPA’s binding to ssDNA. Scientific Reports. 5: 9296.
Le, S., Chen, H, Zhang, X., Chen, J., Patil, K., Muniyappa, K. and Yan, J. (2014). Mechanical force antagonizes the inhibitory effects of RecX on RecA filament formation in Mycobacterium tuberculosis. Nucleic Acids Research, 42: 11992-11999.
Fu, H.X., Le, S.M., Muniyappa, K., and Yan, J. (2013). Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA. PLoS ONE. 8(11): e66712.
Fu, H.X., Le, S.M., Chen, H., Muniyappa, K., and Yan, J. (2013). Force and ATP hydrolysis dependent regulation of RecA nucleoprotein filament by single-stranded DNA binding protein. Nucleic Acids Research. 41(2):924-932.