Professor Sir Shankar Balasubramanian FMedSci FRS | Page 18 | Yusuf Hamied Department of Chemistry

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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

Diversity of Human Copy Number Variation and Multicopy Genes

PH Sudmant, JO Kitzman, F Antonacci, C Alkan, M Malig, A Tsalenko, N Sampas, L Bruhn, J Shendure, 1000 Genomes Project, EE Eichler

– Science

(2010)

330,

641

(doi: 10.1126/science.1197005)

Correction to 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,

546

(doi: 10.1021/ml100241w)

Small-molecule-mediated G-quadruplex isolation from human cells

S Müller, S Kumari, R Rodriguez, S Balasubramanian

– Nature Chemistry

(2010)

2,

1095

(doi: 10.1038/NCHEM.842)

Distinct functions of maternal and somatic Pat1 protein paralogs

A Marnef, M Maldonado, A Bugaut, S Balasubramanian, M Kress, D Weil, N Standart

– RNA (New York, N.Y.)

(2010)

16,

2094

(doi: 10.1261/rna.2295410)

The BCL-2 5′ Untranslated Region Contains an RNA G-Quadruplex-Forming Motif That Modulates Protein Expression

R Shahid, A Bugaut, S Balasubramanian

– Biochemistry

(2010)

49,

8300

(doi: 10.1021/bi100957h)

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 Med Chem Lett

(2010)

1,

306

(doi: 10.1021/ml100062z)

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 and Biomolecular Chemistry

(2010)

8,

2771

(doi: 10.1039/c002418j)

RNA Conformation in Catalytically Active Human Telomerase

JA Yeoman, A Orte, B Ashbridge, D Klenerman, S Balasubramanian

– Journal of the American Chemical Society

(2010)

132,

2852

(doi: 10.1021/ja909383n)

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

– Chem Commun (Camb)

(2009)

46,

946

(doi: 10.1039/b920680a)

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,

10858

(doi: 10.1021/bi901373e)