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Department of Chemistry

 
Portrait of sb10031

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. 


To hear Shankar Balasubramanian discuss some of the group's research click here:


 http://www.sms.cam.ac.uk/media/1111642

Publications

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,
1258
DNA G-quadruplex structures mould the DNA methylome
S-Q Mao, AT Ghanbarian, J Spiegel, S Martínez Cuesta, D Beraldi, M Di Antonio, G Marsico, R Hänsel-Hertsch, D Tannahill, S Balasubramanian
– Nature Structural and Molecular Biology
(2018)
25,
951
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 Research
(2018)
46,
11592
Detecting RNA G-Quadruplexes (rG4s) in the Transcriptome
CK Kwok, G Marsico, S Balasubramanian
– Cold Spring Harb Perspect Biol
(2018)
10,
a032284
Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36
MC Chen, R Tippana, NA Demeshkina, P Murat, S Balasubramanian, S Myong, AR Ferré-D'Amaré
– Nature
(2018)
558,
465
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
AJ Parry, M Hoare, D Bihary, R Hänsel-Hertsch, S Smith, K Tomimatsu, E Mannion, A Smith, P D'Santos, IA Russell, S Balasubramanian, H Kimura, SA Samarajiwa, M Narita
– Nature communications
(2018)
9,
1840
Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing
R Hänsel-Hertsch, J Spiegel, G Marsico, D Tannahill, S Balasubramanian
– Nature Protocols
(2018)
13,
551
Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule.
C Marchetti, KG Zyner, SA Ohnmacht, M Robson, SM Haider, JP Morton, G Marsico, T Vo, S Laughlin-Toth, AA Ahmed, G Di Vita, I Pazitna, M Gunaratnam, RJ Besser, ACG Andrade, S Diocou, JA Pike, D Tannahill, RB Pedley, TRJ Evans, WD Wilson, S Balasubramanian, S Neidle
– Journal of Medicinal Chemistry
(2018)
61,
2500
Sequencing 5-Hydroxymethyluracil at Single-Base Resolution
F Kawasaki, S Martínez Cuesta, D Beraldi, A Mahtey, RE Hardisty, M Carrington, S Balasubramanian
– Angew Chem Int Ed Engl
(2018)
57,
9694
Machine learning model for sequence-driven DNA G-quadruplex formation
AB Sahakyan, VS Chambers, G Marsico, T Santner, M Di Antonio, S Balasubramanian
– Scientific reports
(2017)
7,
14535
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Research Group

Research Interest Group

Telephone number

01223 336347

Email address

sb10031@cam.ac.uk