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

Detection, Structure and Function of Modified DNA Bases.
A Hofer, ZJ Liu, S Balasubramanian
J Am Chem Soc
(2019)
141
Whole genome experimental maps of DNA G-quadruplexes in multiple species
G Marsico, VS Chambers, AB Sahakyan, P McCauley, JM Boutell, MD Antonio, S Balasubramanian
Nucleic acids research
(2019)
47
A Photo-responsive Small-Molecule Approach for the Opto-epigenetic Modulation of DNA Methylation
S Mao, H Nguyen, S Stewart, M Kukwikila, S Jones, D Offenbartl-Stiegert, S Beck, S Howorka, S Balasubramanian
Angew Chem Int Ed Engl
(2019)
58
RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs (vol 19, 229, 2018)
P Murat, G Marsico, B Herdy, AT Ghanbarian, G Portella, S Balasubramanian
Genome biology
(2019)
20
RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs.
P Murat, G Marsico, B Herdy, AT Ghanbarian, G Portella, S Balasubramanian
Genome Biol
(2018)
19
Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter.
A Sengar, JJ Vandana, VS Chambers, M Di Antonio, FR Winnerdy, S Balasubramanian, AT Phan
Nucleic Acids Res
(2018)
47
5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells.
E-A Raiber, G Portella, S Martínez Cuesta, R Hardisty, P Murat, Z Li, M Iurlaro, W Dean, J Spindel, D Beraldi, Z Liu, MA Dawson, W Reik, S Balasubramanian
Nature chemistry
(2018)
10
DNA G-quadruplex structures mould the DNA methylome
S Balasubramanian, S Mao, A Ghanbarian, J Spiegel, S Martinez Cuesta, D Beraldi, M Di Antonio, R Hansel-Hertsch, D Tannahill
Nat Struct Mol Biol
(2018)
25
Analysis of NRAS RNA G-quadruplex binding proteins reveals DDX3X as a novel interactor of cellular G-quadruplex containing transcripts
B Herdy, C Mayer, D Varshney, G Marsico, P Murat, C Taylor, C D'Santos, D Tannahill, S Balasubramanian
Nucleic Acids Res
(2018)
46
Sequencing 5-hydroxymethyluracil at single-base resolution
F Kawasaki, S Martínez Cuesta, D Beraldi, A Mahtey, RE Hardisty, M Carrington, S Balasubramanian
Angewandte Chemie - International Edition
(2018)
57

Research Group

Research Interest Group

Telephone number

01223 336347

Email address