Professor Sir Shankar Balasubramanian FMedSci FRS

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

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

J Am Chem Soc

(2009)

131

12522

(doi: 10.1021/ja903408r)

G-quadruplex nucleic acids as therapeutic targets.

S Balasubramanian, S Neidle

Current Opinion in Chemical Biology

(2009)

345

(doi: 10.1016/j.cbpa.2009.04.637)

Controlled-folding of a small molecule modulates DNA G-quadruplex recognition

S Müller, GD Pantoş, R Rodriguez, S Balasubramanian

Chemical communications (Cambridge, England)

(2008)

(doi: 10.1039/b816861j)

Position and Stability Are Determining Factors for Translation Repression by an RNA G-Quadruplex-Forming Sequence within the 5′ UTR of the NRAS Proto-oncogene

S Kumari, A Bugaut, S Balasubramanian

Biochemistry

(2008)

12664

(doi: 10.1021/bi8010797)

Accurate whole human genome sequencing using reversible terminator chemistry

DR Bentley, S Balasubramanian, HP Swerdlow, GP Smith, J Milton, CG Brown, KP Hall, DJ Evers, CL Barnes, HR Bignell, JM Boutell, J Bryant, RJ Carter, R Keira Cheetham, AJ Cox, DJ Ellis, MR Flatbush, NA Gormley, SJ Humphray, LJ Irving, MS Karbelashvili, SM Kirk, H Li, X Liu, KS Maisinger, LJ Murray, B Obradovic, T Ost, ML Parkinson, MR Pratt, IMJ Rasolonjatovo, MT Reed, R Rigatti, C Rodighiero, MT Ross, A Sabot, SV Sankar, A Scally, GP Schroth, ME Smith, VP Smith, A Spiridou, PE Torrance, SS Tzonev, EH Vermaas, K Walter, X Wu, L Zhang, MD Alam, C Anastasi, IC Aniebo, DMD Bailey, IR Bancarz, S Banerjee, SG Barbour, PA Baybayan, VA Benoit, KF Benson, C Bevis, PJ Black, A Boodhun, JS Brennan, JA Bridgham, RC Brown, AA Brown, DH Buermann, AA Bundu, JC Burrows, NP Carter, N Castillo, M Chiara E Catenazzi, S Chang, R Neil Cooley, NR Crake, OO Dada, KD Diakoumakos, B Dominguez-Fernandez, DJ Earnshaw, UC Egbujor, DW Elmore, SS Etchin, MR Ewan, M Fedurco, LJ Fraser, KV Fuentes Fajardo, W Scott Furey, D George, KJ Gietzen, CP Goddard, GS Golda, PA Granieri, DE Green, DL Gustafson, NF Hansen, K Harnish, CD Haudenschild, NI Heyer, MM Hims, JT Ho, AM Horgan, K Hoschler, S Hurwitz, DV Ivanov, MQ Johnson, T James, TA Huw Jones, G-D Kang, TH Kerelska, AD Kersey, I Khrebtukova, AP Kindwall, Z Kingsbury, PI Kokko-Gonzales, A Kumar, MA Laurent, CT Lawley, SE Lee, X Lee, AK Liao, JA Loch, M Lok, S Luo, RM Mammen, JW Martin, PG McCauley, P McNitt, P Mehta, KW Moon, JW Mullens, T Newington, Z Ning, B Ling Ng, SM Novo, MJ O'Neill, MA Osborne, A Osnowski, O Ostadan, LL Paraschos, L Pickering, AC Pike, AC Pike, D Chris Pinkard, DP Pliskin, J Podhasky, VJ Quijano, C Raczy, VH Rae, SR Rawlings, A Chiva Rodriguez, PM Roe, J Rogers, MC Rogert Bacigalupo, N Romanov, A Romieu, RK Roth, NJ Rourke, ST Ruediger, E Rusman, RM Sanches-Kuiper, MR Schenker, JM Seoane, RJ Shaw, MK Shiver, SW Short, NL Sizto, JP Sluis, MA Smith, J Ernest Sohna Sohna, EJ Spence, K Stevens, N Sutton, L Szajkowski, CL Tregidgo, G Turcatti, S Vandevondele, Y Verhovsky, SM Virk, S Wakelin, GC Walcott, J Wang, GJ Worsley, J Yan, L Yau, M Zuerlein, J Rogers, JC Mullikin, ME Hurles, NJ McCooke, JS West, FL Oaks, PL Lundberg, D Klenerman, R Durbin, AJ Smith

Nature

(2008)

456

(doi: 10.1038/nature07517)

Diarylethynyl amides that recognize the parallel conformation of genomic promoter DNA G-quadruplexes.

J Dash, PS Shirude, S-TD Hsu, S Balasubramanian

Journal of the American Chemical Society

(2008)

130

15950

(doi: 10.1021/ja8046552)

A Novel Small Molecule That Alters Shelterin Integrity and Triggers a DNA-Damage Response at Telomeres