|The overall goal of my research group is to employ cutting-edge biophysical techniques 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. We aim to use the fundamental knowledge to fight neurodegenerative diseases, cancers, bacterial and viral infections by designing and discovering novel therapeutic ligands targeting RNA. To approach the challenging goals, we have assembled a multidisciplinary team with expertise ranging from molecular biophysics, structure biology, computation, chemical synthesis, cell biology, to medical healthcare. 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,
(3) designing and discovering therapeutic ligands (small molecules, oligonucleotides, peptides, peptide nucleic acid, etc.) targeting RNA,
(4) developing nucleic acid based biosensors to rapidly detect toxic/pathogenic agents in food products and human body, and
(5) discovering and characterizing novel nucleic acid based catalysts for important organic and inorganic reactions at mild conditions.
We employ various conventional and cutting-edge biophysical and biochemical techniques including laser optical tweezers, NMR, UV-Vis, fluorescence, SPR, gel electrophoresis, PCR, chemical synthesis of modified oligonucleotides and peptides, in vitro transcription, protein expression, and cell culture assay. 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.
Selected Representative Publications:
Zhou, Y., Kierzek, E., Loo, Z.P., Antonio, M., Yau, Y.H., Chuah, Y.W., Geifman-Shochat, S., Kierzek, R., and Chen, G. (2013) Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. Nucleic Acids Res, doi: 10.1093/nar/gkt352
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
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)
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.
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.
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)
- Solid State Nanopore Devices for Single Molecule Biophysics and Sequencing
- Start Up Grant
- Targeting RNA Duplexes With Modified Triplex-Forming Oligonucleotides: From Atomic Mutation to Single-Molecule Manipulation
- Zhou, Y., Kierzek, E., Loo, Z.P., Antonio, M., Yau, Y.H., Chuah, Y.W., Geifman-Shochat, S., Kierzek, R., and Chen, G. (2013). Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. doi: 10.1093/nar/gkt352. Nucleic Acids Research, .