Herchel Smith Professor of Medicinal 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 and genomics. 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. 

Hear Shankar Balasubramanian discuss some of the group's research.

Watch Professor Balasubramanian discuss his research

Take a tour of the Balasubramanian Lab

Publications

Targeting the c-Kit Promoter G-quadruplexes with 6-Substituted Indenoisoquinolines.
M Bejugam, M Gunaratnam, S Müller, DA Sanders, S Sewitz, JA Fletcher, S Neidle, S Balasubramanian
ACS Medicinal Chemistry Letters
(2010)
1
Small molecule-mediated inhibition of translation by targeting a native RNA G-quadruplex.
A Bugaut, R Rodriguez, S Kumari, S-TD Hsu, S Balasubramanian
Organic & Biomolecular Chemistry
(2010)
8
RNA conformation in catalytically active human telomerase.
JA Yeoman, A Orte, B Ashbridge, D Klenerman, S Balasubramanian
J Am Chem Soc
(2010)
132
Ensemble and single molecule FRET analysis of the structure and unfolding kinetics of the c-kit promoter quadruplexes.
A Fegan, PS Shirude, L Ying, S Balasubramanian
Chemical communications (Cambridge, England)
(2009)
46
Single-Molecule Analysis of the Human Telomerase RNA·Dyskerin Interaction and the Effect of Dyskeratosis Congenita Mutations
B Ashbridge, A Orte, JA Yeoman, M Kirwan, T Vulliamy, I Dokal, D Klenerman, S Balasubramanian
Biochemistry
(2009)
48
Genome-wide analysis of a G-quadruplex-specific single-chain antibody that regulates gene expression
H Fernando, S Sewitz, J Darot, S Tavaré, JL Huppert, S Balasubramanian
Nucleic Acids Res
(2009)
37
LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans.
NJ Lehrbach, J Armisen, HL Lightfoot, KJ Murfitt, A Bugaut, S Balasubramanian, EA Miska
Nature Structural & Molecular Biology
(2009)
16
A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics
S-TD Hsu, P Varnai, A Bugaut, AP Reszka, S Neidle, S Balasubramanian
J Am Chem Soc
(2009)
131
A Small Molecule That Disrupts G-Quadruplex DNA Structure and Enhances Gene Expression
ZAE Waller, SA Sewitz, S-TD Hsu, S Balasubramanian
Journal of the American Chemical Society
(2009)
131
G-quadruplex DNA bound by a synthetic ligand is highly dynamic.
PV Jena, PS Shirude, B Okumus, K Laxmi-Reddy, F Godde, I Huc, S Balasubramanian, T Ha
Journal of the American Chemical Society
(2009)
131

Research Group

Research Interest Group

Telephone number

01223 336347

Email address