|Asst Prof Curtis Alexander Davey|
Division of Structural Biology & Biochemistry
School of Biological Sciences
College of Science
- PhD University of Miami 1996
- BA(Psychol) University of Colorado 1991
- BA(Biochem) University of Colorado 1991
|Assistant Professor, 2004-present
Division of Structural and Computational Biology, School of Biological Sciences
Nanyang Technological University [Singapore]
Staff Scientist (Oberassistent), 2003
Post-Doctoral Fellow, 1998-2002
ETH-Zürich, Institute of Molecular Biology & Biophysics [Switzerland]
Post-Doctoral Fellow, 1996-1997
University of Miami, Dept. of Chemistry [USA]
Ph.D. in Biochemistry & Molecular Biology, 1991-1996
University of Miami School of Medicine, Dept. of Biochemistry & Molecular Biology [USA]
B.A. in Biochemistry, 1987-1991
University of Colorado [Boulder, USA]
B.A. in Psychology, 1987-1991
University of Colorado [Boulder, USA]
* B. Wu & C.A. Davey. 2008. Platinum Drug Adduct Formation in the Nucleosome Core Alters Nucleosome Mobility but not Positioning. Chem. Biol. (Cell Press). 15(10): 1023-1028.
* G.E. Davey & C.A. Davey. 2008. Chromatin– a New, Old Drug Target? Chem. Biol. Drug Des. 72(3): 165-170.
* B. Wu, P. Dröge & C.A. Davey. 2008. Site Selectivity of Platinum Anticancer Therapeutics. Nature Chem. Biol. 4(2): 110-112.
> “Platinum Result” in Research Highlights. 2008. Nature. 451(7175): 111.
* P. Dröge & C.A. Davey. 2008. Do Cells let-7 Determine Stemness? Cell Stem Cell (Cell Press). 2(1): 8-9.
* M.S. Ong, T.J. Richmond & C.A. Davey. 2007. DNA Stretching and Extreme Kinking in the Nucleosome Core. J. Mol. Biol. 368(4): 1067-1074.
* Q. Bao, H. Chen, Y. Liu, J. Yan, P. Dröge & C.A. Davey. 2007. A Divalent Metal-mediated Switch Controlling Protein-induced DNA Bending. J. Mol. Biol. 367: 731-740.
* O. Li, D. Vasudevan, C.A. Davey & P. Dröge. 2006. High-Level Expression of DNA Architectural Factor HMGA2 and Its Association with Nucleosomes in Human Embryonic Stem Cells. Genesis. 44(11): 523-529.
* T.J. Richmond & C.A. Davey. 2003. The Structure of DNA in the Nucleosome Core. Nature. 423(6936): 145-150.
|DNA in eukaryotic cells is packaged by histone proteins into chromatin, a dynamic hierarchical organization underlying genomic function. The basic chromatin building block is the nucleosome core particle, in which ~147 base pairs of DNA are wrapped in 1 & 2/3 superhelical turns around a histone protein octamer. Our high resolution crystallographic analysis of the nucleosome core particle yielded a wealth of insight into histone-DNA association. In fact, the conformation of DNA in the nucleosome core is remarkably different than its naked form or that associated with other nuclear proteins and is dependent on both DNA sequence and positioning on the histone octamer. We found that even divalent metal hydrates can recognize this unique feature of the nucleosome, binding in a DNA sequence- and orientation-selective manner.
Our present goal is to find new drug targets and develop novel therapeutics by studying DNA structure and chemistry within a physiological framework. Approximately 83% of genomic DNA is associated with histone octamers, rendering the nucleosome core an important therapeutic target. However, relatively little is known about the influence of histone packaging on DNA-drug interaction. Since nucleosomal DNA displays sequence- and context-dependent structural features that can be recognized by even simple small molecules, the main premise of our present investigations is to explore the possibilities for nucleosome-selective recognition by medicinal agents and nuclear protein factors. The discovery of nucleosome-specific compounds would hold promise for the acquisition of improved therapeutic agents by allowing for a level of site discrimination beyond the primary structure of DNA.
|Research Grant |
- A*STAR Biomedical Research Council (2007-)
- Academic Research Fund Tier 1 (2012-)
- National Medical Research Council (2011-)
|Current Projects |
- Molecular Targeting and Mechanism of Action of Ruthenium Anticancer Agents
- Platinum Anticancer Drug Site Selectivity & Mechanism
- Structural Characterization of the p53 Tumour Suppressor Protein Bound to the Nucleosome
- Structural studies on the interaction of the chromatin-unfolding high mobility group N proteins and peptides with the nucleosome core particle
- Davey, C.A. (2013). Does the Nucleosome Break Its Own Rules?. Current opinion in structural biology, .
- 2.S.M. Meier, M. Hanif, Z. Adhireksan, V. Pichler, M. Novak, E. Jirkovsky, M.A. Jakupec, V.B. Arion, C.A. Davey, B.K. Keppler & C.G. Hartinger. (2013). Novel Metal(II) Arene 2-Pyridinecarbothioamides: A Rational to Orally Active Organometallic Anticancer Agents.. Chemical Science, .
- Chua EY, Vasudevan D, Davey GE, Wu B, Davey CA. (2012). The mechanics behind DNA sequence-dependent properties of the nucleosome.. Nucleic Acids Research, .
- Wu B, Davey GE, Nazarov, AA, Dyson PJ, Davey CA. (2011). Specific DNA Structural Attributes Modulate Platinum Anticancer Drug Site Selection and Cross-Link Generation. Nucleic Acids Research, 39(18), 8200-12.
- Abdollah Allahverdi, Renliang Yang, Nikolay Korolev, Yanping Fan, Curt A. Davey, Chuan-Fa Liu and Lars Nordenskiold. (2011). The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association. Nucleic Acids Research, 39, 1680–1691.