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 and medicine. Projects are inherently interdisciplinary and will provide scope for a diversity of intellectual and experimental approaches that include: organic synthesis, biophysics, molecular and cellular biology. Our scientific goals are problem-driven, which constantly raises the need to invent new methodology.

A major interest is to elucidate and manipulate mechanisms that control the expression of genes (either transcription, or translation). We are particularly interested in the role of non-canonical nucleic acid structures that control gene expression (e.g. G-quadruplexes, micro RNA and RNA structures in the 5' untranslated regions of mRNAs). Our goal is to design and synthesise small organic molecules that target such structures and alter the expression of certain genes of interest. Such small molecule gene regulators are valuable tools to study mechanisms in biology and will also open up new approaches for therapeutics and molecular medicine, particularly for diseases characterized by aberrant expression of certain genes (e.g. various cancers).

Our fundamental science will inevitably create opportunities for translation and commercialisation. One such example was our invention (with Professor David Klenerman) of new DNA sequencing technology ("Solexa sequencing") that was commercialised as a Cambridge University spinout company (now part of Illumina Inc.) and is used routinely for applications in genomics, including human genome sequencing.

Selected Publications

(for full list see http://www-shankar.ch.cam.ac.uk/ )

A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA- Damage Response at Telomeres
R Rodriguez, S Muller, J A Yeoman, C Trentesaux, J-F Riou and S Balasubramanian
J Am Chem Soc, 130, 15758-15759 (2008)

Single-molecule analysis of human telomerase monomer
D Alves, H Li, R Codrington, A Orte, X Ren, D Klenerman and S Balasubramanian
Nature Chem Biol, 4, 287-289 (2008)

Exploring the differential recognition of DNA G-quadruplex targets by small molecules using dynamic combinatorial chemistry
A Bugaut, K Jantos, J-L Wietor, R Rodriguez, J K M Sanders and S Balasubramanian
Angew Chem Int Ed, 47, 2677-2680 (2008)

Trisubstituted Isoalloxazines as a New Class of G-Quadruplex Binding Ligands: Small Molecule Regulation of c-kit Oncogene Expression
M Bejugam, S Sewitz, P S Shirude, R Rodriguez, R Shahid and S Balasubramanian
J Am Chem Soc, 129, 12926-12927 (2007)

An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene moldulates translation
S Kumari, A Bugaut, J L Huppert and S Balasubramanian
Nature Chem Biol, 3, 218-221 (2007)