研究领域

Biological

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.

近期论文

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Formation and Abundance of 5-Hydroxymethylcytosine in RNA. SM Huber, P van Delft, L Mendil, M Bachman, K Smollett, F Werner, EA Miska, S Balasubramanian – Chembiochem (2015) n/a (DOI: 10.1002/cbic.201500013) Insights into the mechanism of a G-quadruplex-unwinding DEAH-box helicase. MC Chen, P Murat, K Abecassis, AR Ferré-D'Amaré, S Balasubramanian – Nucleic acids research (2015) 43, 2223 (DOI: 10.1093/nar/gkv051) Decoding genomes S Balasubramanian – Biochemical Society Transactions (2015) 43, 1 (DOI: 10.1042/bst20140254) Accurate Measurement of 5-Methylcytosine and 5-Hydroxymethylcytosine in Human Cerebellum DNA by Oxidative Bisulfite on an Array (OxBS-Array). SF Field, D Beraldi, M Bachman, SK Stewart, S Beck, S Balasubramanian – PLoS One (2015) 10, e0118202 (DOI: 10.1371/journal.pone.0118202) The biology and genomic localization of cytosine modifications GR McInroy, NM Bell, G Ficz, S Balasubramanian, W Reik, E-A Raiber – Epigenetics and Human Health (2015) 4, 167 (DOI: 10.1007/978-3-642-31974-7_8) 5-Formylcytosine alters the structure of the DNA double helix. EA Raiber, P Murat, DY Chirgadze, D Beraldi, BF Luisi, S Balasubramanian – Nature Structural & Molecular Biology (2014) 22, 44 (DOI: 10.1038/nsmb.2936) 5-Hydroxymethylcytosine is a predominantly stable DNA modification M Bachman, S Uribe-Lewis, X Yang, M Williams, A Murrell, S Balasubramanian – Nature Chemistry (2014) 6, 1049 (DOI: 10.1038/nchem.2064) Dual binding of an antibody and a small molecule increases the stability of TERRA G-quadruplex. PM Yangyuoru, M Di Antonio, C Ghimire, G Biffi, S Balasubramanian, H Mao – Angew Chem Int Ed Engl (2015) 54, 910 (DOI: 10.1002/anie.201408113) Solexa sequencing: decoding genomes on a population scale. S Balasubramanian – Clinical Chemistry (2015) 61, 21 (DOI: 10.1373/clinchem.2014.221747) Targeting DNA G-Quadruplexes with Helical Small Molecules S Müller, K Laxmi-Reddy, PV Jena, B Baptiste, Z Dong, F Godde, T Ha, R Rodriguez, S Balasubramanian, I Huc – Chembiochem (2014) 15, 2563 (DOI: 10.1002/cbic.201402439) Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells. D Schiavone, G Guilbaud, P Murat, C Papadopoulou, P Sarkies, MN Prioleau, S Balasubramanian, JE Sale – EMBO Journal (2014) 33, 2507 (DOI: 10.15252/embj.201488398) Chemical biology of genomic DNA: minimizing PCR bias GR McInroy, EA Raiber, S Balasubramanian – Chemical communications (Cambridge, England) (2014) 50, 12047 (DOI: 10.1039/c4cc05107f) oxBS-450K: A method for analysing hydroxymethylation using 450K BeadChips. SK Stewart, TJ Morris, P Guilhamon, H Bulstrode, M Bachman, S Balasubramanian, S Beck – Methods (2015) 72, 9 (DOI: 10.1016/j.ymeth.2014.08.009) Nucleotide Contributions to the Structural Integrity and DNA Replication Initiation Activity of Noncoding Y RNA I Wang, MP Kowalski, AR Langley, R Rodriguez, S Balasubramanian, ST Hsu, T Krude – Biochemistry (2014) 53, 5848 (DOI: 10.1021/bi500470b) Chemical Methods for Decoding Cytosine Modifications in DNA. MJ Booth, EA Raiber, S Balasubramanian – Chem Rev (2014) 140929121453004 (DOI: 10.1021/cr5002904) Chemical biology on the genome S Balasubramanian – Bioorganic & medicinal chemistry (2014) 22, 4356 (DOI: 10.1016/j.bmc.2014.05.016) Quantitative sequencing of 5-formylcytosine in DNA at single-base resolution MJ Booth, G Marsico, M Bachman, D Beraldi, S Balasubramanian – Nature Chemistry (2014) 6, 435 (DOI: 10.1038/NCHEM.1893) Reprogramming the Mechanism of Action of Chlorambucil by Coupling to a G-Quadruplex Ligand M Di Antonio, KI McLuckie, S Balasubramanian – Journal of the American Chemical Society (2014) 136, 5860 (DOI: 10.1021/ja5014344) G-quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation. P Murat, J Zhong, L Lekieffre, NP Cowieson, JL Clancy, T Preiss, S Balasubramanian, R Khanna, J Tellam – Nature Chemical Biology (2014) 10, 358 (DOI: 10.1038/nchembio.1479) Targeting a c-MYC G-quadruplex DNA with a fragment library HR Nasiri, NM Bell, KI McLuckie, J Husby, C Abell, S Neidle, S Balasubramanian – Chemical communications (Cambridge, England) (2014) 50, 1704 (DOI: 10.1039/c3cc48390h)