Professor Sir Shankar Balasubramanian
Professor Sir Shankar Balasubramanian is pleased to consider applications from prospective PhD students.
We are interested in the chemical biology of nucleic acids and the genome. Our research explores the sequence, structure and function of DNA and RNA. We have been exploring four stranded structures, called G-quadruplexes, that can form from particular G-rich sequences in DNA and RNA. Such folded structures are stable and there is accumulating evidence to support that G-quadruplex sequence motifs have an associated function in telomere biology, and the control of gene expression at transcriptional and translational levels. Small molecules that stabilise such structures can interfere with telomere biology and the transcription of genes. We are adapting these principles to evaluate whether certain molecules have anti-cancer potential.
We are also exploring the chemistry and function of non-canonical DNA bases that include 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) each of which is present in the DNA of mammals. There is evidence to suggest these modified bases may each mark distinct function(s) in the genome that relate to normal biology and disease. We have developed chemistry to sequence 5mC, 5hmC and 5fC in genomic DNA.
cell culture; bioinformatics; computational modelling; confocal microscopy; DNA sequencing; fluorescence microscopy; gene expression profiling; genomics; HPLC/FPLC; PCR
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M Bachman, S Uribe-Lewis, X Yang, H E Burgess, M Iurlaro, W Reik and S Balasubramanian, 5-Formylcytosine can be a stable DNA modification in mammals, Nature Chemical Biology, 2015, 11, 555 - 557, DOI: 10.1038/nchembio.1848
V S Chambers, G Marsico, J M Boutell, M Di Antonio, G P Smith and S Balasubramanian, High-throughput sequencing of DNA G-quadruplex structures in the human genome, Nature Biotechnology, 2015, 33, 877 - 881, DOI: 10.1038/nbt.3295
E Raiber, P Murat, D Y Chirgadze, D Beraldi, B F Luisi and S Balasubramanian, 5-Formylcytosine alters the structure of the DNA double helix, Nature Structural & Molecular Biology, 2015, 22, 44 - 49, DOI: 10.1038/nchembio.1848
P Murat, J Zhong, L Lekieffre, N P Cowieson, J L Clancy, T Preiss, S Balasubramanian, R Khanna and J Tellam, G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation, Nature Chemical Biology, 2014, 10, 358 - 364, DOI:10.1038/nchembio.1479
M J Booth, G Marsico, M Bachman, D Beraldi and S Balasubramanian, Quantitative sequencing of 5-formylcytosine in DNA at single-base resolution, Nature Chemistry, 2014, 6, 435 - 440, DOI:10.1038/nchem.1893
G Biffi, D Tannahill, J McCafferty and S Balasubramanian, Quantitative visualization of DNA G-quadruplex structures in human cells, Nature Chemistry, 2013, 5, 182-186, DOI: 10.1038/nchem.1548 M J Booth, T W B Ost, D Beraldi, N Bell, M Branco, W Reik and S Balasubramanian, Oxidative Bisulfite sequencing of 5-methylcytosine and 5-hydroxymethlcytosine, Nature Protocols, 2013, 8, 1841 - 1851, DOI: 10.1038/nprot.2013.115
M J Booth, M R Branco, G Ficz, D Oxley, F Krueger, W Reik and S Balasubramanian, Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution, Science, 2012, 336, 934 - 937, DOI: 10.1126/science.1220671
R Rodriguez, K M Miller, J V Forment, C R Bradshaw, M Nikan, S Britton, T Oelschlaegel, B Xhemalce, S Balasubramanian and S P Jackson, Small-molecule-induced DNA damage identifies alternative DNA structures in human genes, Nat. Chem. Biol., 2012, 8, 301-10, DOI: 10.1038/nchembio.780
M Bejugam, S Sewitz, P S Shirude, R Rodriguez, R Shahid and S Balasubramanian, Trisubstituted Isoalloxazines as a New Class of G-Quadruplex Binding Ligands: Small Molecule Regulation of c-kit Oncogene Expression, J. Am. Chem. Soc., 2007, 129, 12926-12927, DOI: 10.1021/ja075881p
S Kumari, A Bugaut, J L Huppert and S Balasubramanian, An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation, Nature Chemical Biology, 2007, 3, 218-221, DOI: 10.1038/nchembio864
J L Huppert and S Balasubramanian, Prevalence of quadruplexes in the human genome, Nucleic Acids Res., 2005, 33, 2908-2916, DOI: 10.1093/nar/gki609