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CHEN, Gang

Assistant Professor

Education: B.Sc., University of Science and Technology of China (USTC); Ph.D., University of Rochester; Post-doc: University of California, Berkeley, The Scripps Research Institute

Research Area: Biophysical Chemistry; Single-Molecule Detection and Nanomanipulation; RNA Structures, Properties, and Functions; Therapeutics Targeting RNA and RNA-protein complex.

Phone: (65) 6592 2549

E-mail: rnachen@ntu.edu.sg


Research Interest

The functions of RNA include coding (for protein, RNA, and DNA), gene regulation, catalysis, and immunomodulation. The overall goal of Gang CHEN research group is to better understand the structures and the physical-chemical properties of RNAs and RNA-ligand complexes to provide deeper insight into and to facilitate precise control of the diverse biological functions involving RNA. The research projects of current interests are: (1) characterizing the molecular recognition interactions (e.g., hydrogen bonding and aromatic base stacking) accounting for structure, stability, and dynamics of RNA structural building blocks such as internal loops, hairpins, triplexes, and pseudoknots, (2) probing the complex energy landscapes of RNA folding and assembly with protein, and (3) designing and discovering therapeutic ligands (small molecules, oligonucleotides, peptides, and peptide nucleic acids) targeting RNA and RNA-protein complex.
We employ various conventional and cutting-edge biophysical, biochemical, and bioorganic techniques including single-molecule nano-manipulation using laser optical tweezers, NMR, UV-Vis, AFM, bulk and single-molecule fluorescence, SPR, ITC, chemical synthesis of modified oligonucleotides and peptides, PCR, gel electrophoresis, in vitro transcription and translation, and protein expression and purification. The research experience in the laboratory will help the students to grasp fundamental knowledge and experimental skills, to develop learning skills such as rigorous reasoning and innovative thinking, and to be able to ask and answer important questions within and beyond chemical and molecular sciences.

Many viruses including HIV-1, SARS-CoV, and some agriculturally important plant viruses have evolved programmed ribosomal frameshift to express defined ratios of structural and enzymatic proteins. Highly efficient frameshift at an mRNA slippery sequence from X XXY YYZ (0 frame) to XXX YYY Z (–1 frame) is often stimulated by a down-stream mRNA structure, e.g., pstudoknot.

Innate immune response is the first line of defense of host cells in mammals against virus infection. The discoveries concerning the activation of innate immunity were awarded the Nobel Prize in Physiology or Medicine in 2011. One major type of innate immune receptors, Toll-like receptors, have been the targets of nucleic acid vaccine adjuvants in clinical trials. RIG-I is a newly discovered cytosolic pattern-recognition receptor that senses viral RNAs released from replicating viruses in infected cells. (Left) Crystal structure (PDB: 3NCU) of the RIG-I C-terminal domain (CTD) (shown in blue) in complex with a 12-bp dsRNA with 5′-pp. RIG-I CTDs are bound to both ends of the dsRNA. (Right) Crystal structure (PDB: 2YKG) of the two-domain RIG-I helicase-CTD in complex with a 10-bp dsRNA with 5′-OH. RIG-I CTD is bound to one terminal end of the dsRNA, with the helicase domain wrapping around the dsRNA.

Selected Representative Publications

  1. Zhou, Y., Kierzek, E., Loo, Z.P., Antonio, M., Yau, Y.H., Geifman-Shochat, S., Kierzek, R., and Chen, G. (2012) Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. Submitted

  2. Tinoco, I., Jr., Chen, G., and Qu, X. (2010) RNA reactions one molecule at a time, in RNA Worlds, (Gesteland, R.F., Cech, T.R., and Atkins, J.F., Eds.), Cold Spring Harbor Laboratory Press. Cold Spring Harb Perspect Biol. doi: 10.1101/cshperspect.a003624

  3. Chen, G., Chang, K.-Y., Chou, M.-Y., Bustamante, C., and Tinoco, I., Jr. (2009) Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of –1 ribosomal frameshifting. Proc. Natl. Acad. Sci. USA 106, 12706-11. (Cover Highlight and In This Issue Highlight) .

  4. Chen, G., Wen, J.-D., and Tinoco, I., Jr. (2007) Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA. RNA 13, 2175-88.

  5. Chen, G., Kennedy, S.D., and Turner, D.H. (2009) A CA+ pair adjacent to a sheared GA or AA pair stabilizes size-symmetric RNA internal loops. Biochemistry 48, 5738-52.

  6. Chen, G., Znosko, B.M., Kennedy, S.D., Krugh, T.R., and Turner, D.H. (2005) Solution structure of an RNA internal loop with three consecutive sheared GA pairs. Biochemistry 44, 2845-56. (Listed as one of five "Hot Articles" in Feb. 2005 in Biochemistry)