Research Guides

Tom Brown

Head of Nucleic Acids Research Group

We design and synthesise chemically modified DNA for diagnostic and therapeutic applications

Website: http://www.browngroupnucleicacidsresearch.org.uk/

I am a member of the Departments of Chemistry and Oncology and my research interests centre on nucleic acid chemistry and its applications in biology, diagnostics and medicine. Using X-ray crystallography and NMR we have studied the nature of base mispairing in DNA, the structure of DNA duplexes containing mutagenic lesions and the interaction of DNA with repair enzymes. We have developed rapid methods for the identification of mutations in the human genome, the best example being Scorpions which are used to analyse genomic DNA at single base resolution. Scorpions were developed in collaboration with AstraZeneca and are used in companion diagnostics. They have led to the clinical use of several cancer drugs which were previously rejected on the basis of limited efficacy. We also work on the chemical synthesis of DNA analogues for therapeutic applications including chemically modified aptamers to target cancer cells with the aim of delivering drugs, and we are developing CRISPR-based systems for cellular imaging and editing. We have developed a number of artificial DNA/RNA backbones that can be read through by polymerase enzymes and this led us to develop chemical methods of nucleic acid ligation and gene synthesis. The long term aim is to assemble therapeutic mRNAs on a large scale and to manipulate the genetic code.

I am the co-founder of three Biotech companies and have published over 360 research papers.

External Appointments and Recognition

I have received the Royal Society of Edinburgh MakDougall-Brisbane prize for research, the Royal Society of Edinburgh Caledonian Research Fellowship, the Royal Society Leverhulme Senior Research Fellowship, the Royal Society of Chemistry Josef Loschmidt prize, the Royal Society of Chemistry award for Nucleic Acid Chemistry and the Royal Society of Chemistry prize for Interdisciplinary Research, Chemistry World Entrepreneur of the Year and BBSRC Innovator of the Year. 

I am a Fellow of the Royal Society of Edinburgh, a Fellow of the Royal Society of Chemistry, outgoing President of the Chemical Biology Interface Division committee of the Royal Society of Chemistry,  a member of the editorial board of Chemistry World and co-Chair of EuCheMs 2018.

Further information

Research group web site:

www.browngroupnucleicacidsresearch.org.uk

Chemistry World Entrepreneur of the Year:

http://www.rsc.org/chemistryworld/2014/05/entrepreneur-2014-tom-brown/

BBSRC Innovator of the Year:

http://www.bbsrc.ac.uk/news/people-skills-training/2016/160519-n-bioscience-impact-innovation-competition-winners-announced/

Innovative nucleic acid chemistry:

http://www.bbsrc.ac.uk/news/impact/innovative-nucleic-acid-chemistry/

Click DNA ligation:

http://zon.trilinkbiotech.com/2015/04/27/click-chemistry/

Publications

Google Scholar: https://scholar.google.com/citations?user=DanQbhQAAAAJ&hl=en

Researcher id:    http://www.researcherid.com/rid/C-9185-2016

Orcid:                   https://orcid.org/0000-0002-6538-3036

 

10 Selected publications

Kukwikila, M., Gale, N., El-Sagheer, A. H., Brown, T. & Tavassoli, A. Assembly of a biocompatible triazole-linked gene by one-pot click-DNA ligation. Nature Chem., doi:10.1038/NCHEM.2850 (2017).

Hardwick, J. S. et al. 5-Formylcytosine does not change the global structure of DNA. Nature Struct. Mol. Biol., doi:10.1038/nsmb.3411 (2017).

Shivalingam, A., Tyburn, A. E. S., El-Sagheer, A. H. & Brown, T. Molecular Requirements of High-Fidelity Replication-Competent DNA Backbones for Orthogonal Chemical Ligation. J. Amer. Chem. Soc. 139, 1575–1583 (2017).

Haugland, M. M. et al. 2 '-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA. J. Amer. Chem. Soc. 138, 9069-9072, (2016).

Meng, W. et al. An Autonomous Molecular Assembler for Programmable Chemical Synthesis. Nature Chem. 8, 542-548 (2016).

Harimech, P. K., Gerrard, S. R., El-Sagheer, A. H., Brown, T. & Kanaras, A. G. Reversible Ligation of Programmed DNA-Gold Nanoparticle Assemblies. J. Amer. Chem. Soc. 137, 9242-9245, (2015).

El-Sagheer, A. H., Sanzone, A. P., Gao, R., Tavassoli, A. & Brown, T. Biocompatible artificial DNA linker that is read through by DNA polymerases and is functional in E. coli. Proc. Natl. Acad. Sci. USA 108, 11338–11343, (2011).

El-Sagheer, A.H., Brown, T. New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes. Proc. Natl. Acad. Sci. USA 107, 15329-15334, (2010).

El-Sagheer, A. H. & Brown, T. Synthesis and Polymerase Chain Reaction Amplification of DNA Strands Containing an Unnatural Triazole Linkage. J. Amer. Chem. Soc. 131, 3958-3964, (2009).

Whitcombe, D., Theaker, J., Guy, S. P., Brown, T. & Little, S. Detection of PCR products using self-probing amplicons and fluorescence. Nature Biotechnol. 17, 804-807 (1999).