Department of Chemistry

Nucleic acids are fundamental to life. Our research is focused on the chemical biology of nucleic acids, and employs the principles of chemistry and the molecular sciences to address questions of importance in biology. Projects will provide scope for a diversity of intellectual and experimental approaches that include: organic synthesis, molecular biology, biophysics and cell biology.

• Quadruplex Nucleic Acids: DNA adopts the classical double helix structure, but can exist in alternative structural forms. We are investigating the existence and functional relevance of a quadruplex helical form of DNA, called G-quadruplex, which forms from certain guanine-rich sequences that occur throughout genomes. We believe G-quadruplex structures can act as molecular switches that control cell proliferation and the activation of a large number of genes. As part of our studies, we are synthesising molecules that recognize and stabilise the DNA (and RNA) quadruple helix and interfere with specific cellular processes. Such molecules may well hold the key to new therapeutic approaches in numerous areas of human disease that include cancer.
• Telomeres and Telomerase: Telomeres are made up of DNA that protects the ends of the chromosomes in the human genome. Human telomerase is a DNA polymerase enzyme comprising catalytic RNA and catalytic protein that extends the telomeric DNA. Both the enzyme and the telomeres are linked to the process of human ageing and also the mechanism of cancer proliferation. We study the structure and function of the enzyme and the significance of telomere structure and function in living systems.
• Single Molecule Science: The study of single molecules reveals that molecules in a population do not all "look" or "behave" the same way at a given moment in time. Such heterogeneities in properties (e.g. structure and conformation) can be significant in complex. In collaboration with Professor David Klenerman and Dr Liming Ying we are applying fluorescence spectroscopy to interrogate single molecules that include proteins and nucleic acids. This is a relatively new area of science that holds considerable potential for innovation and discovery. In our previous work we invented new DNA sequencing technology (Solexa sequencing) that was commercialised as a Cambridge University spinout company now part of Illumina Inc.

Selected Publications

Quandruplexes

Angew. Chem. Int. Ed., 47, 2677-2680 (2008)

Angew. Chem. Int. Ed., 46, 5404-5407 (2007)

J. Am. Chem. Soc., 129, 11890-11891 (2007)

J. Am. Chem. Soc. , 129, 12926-12927 (2007)

J. Am. Chem. Soc. , 129, 7484-7485 (2007)

Nature Chem. Bio. , 3, 4, 218-221 (2007)

Nucleic Acids Res. , 35, 2, 406-413 (2007)

Biochemistry, 45, 7854-7860 (2006)

J. Am. Chem. Soc., 126, 9809-9812 (2006)

J. Am. Chem. Soc. 127, 10584 - 10589 (2005)

Telomerase

Nature Chem. Bio., 4, 287-289 (2008)

J. Am. Chem. Soc., 128, 4992-5000 (2006)

Biochemistry, 43, 13452-13458 (2004)

Nucleic Acids Res., 31, 6509-6515 (2003)

Single Molecule Science

J. Am. Chem. Soc., 129, 7484-7485 (2007)

Angew. Chem. Int. Ed. , 45, 7540-7543 (2006)

Proc. Natl. Acad. Sci. USA 101, 14425-14430 (2004)

Proc. Natl. Acad. Sci. USA, 100, 14629-14634 (2003)