Engineering and the Environment

Tom Brown

PhD FRSE FRSC

Primary position:
Visiting Professor of Chemical Biology

Background

The University of Southampton

Tom Brown's Publications and Citation Metrics

Tom Brown studied Chemistry at Bradford University where he completed his PhD under the supervision of Gordon Shaw in 1979. He carried out postdoctoral research at Oxford and Cambridge Universities before moving to Edinburgh University in 1985 as a lecturer. In 1995 he moved to Southampton as professor of nucleic acid chemistry and is now professor of Chemical Biology.

In the early part of his academic career Tom studied base pair mismatches and their implications for DNA repair. Notable examples that attracted international attention have appeared in the journal Nature (1985, 315, 604 and 1986, 320, 552). This approach paved the way for the elucidation of the mutagenic effect of chemically modified DNA bases, most importantly the O6-methyl guanine lesion (PNAS 1990, 87, 9573). This was the first time that the origin of a mutation caused by chemical damage to DNA had been explained at the molecular level. This was followed by studies to determine the nature of the recognition of mutagenic bases by DNA repair enzymes, most notably a collaboration with Laurence Pearl to elucidate the structural basis of excision repair by uracil-DNA glycosylases (Nature 1995, 373, 487; Nature Struct. Biol. 1998, 5, 697). The expertise gained from these fundamental studies on DNA base pairing was used to develop new methods of mutation analysis.  In collaboration with AstraZeneca Tom Brown developed a novel technology for the identification of mutations in the human genome (Scorpion Probes). This was one of the first successful methods for rapid mutation detection (Nature Biotechnol. 1999, 17, 804). The resultant patent led to a spin-out from AstraZeneca (DxS Genotyping), which was recently acquired by Qiagen for $120 million. Tom is also co-inventor (with LGC) of "HyBeacon" technology, a novel fluorogenic method that utilises DNA melting as a means to identify mutations. HyBeacons also have clinical applications for the rapid diagnosis of bacterial infections and are being developed in the Forensic field for rapid human identification.

Tom's group has recently developed a click chemistry methodology which has been used to synthesise a DNA catenane (JACS 2007, 129, 6859) and to unravel the DNA binding mechanism of a novel threading intercalator (JACS 2008, 130, 14651). He has also used a related approach to construct large biologically active RNA constructs which are beyond the reach of conventional solid-phase synthesis (PNAS 2010, 107, 15329) and to synthesise DNA templates containing modified triazole backbones which are copied by DNA and RNA polymerases and are functional in vivo (JACS 2009, 131, 3958; PNAS 2011, 108, 11338; Chem. Comm. 2011, 47, 12057). The structural basis of the remarkable biocompatibility of this triazole linkage has recently been elucidated (Chem. Eur J. 2011, 17, 14714). Click nucleic acid ligation is currently being used in the chemical synthesis of genes and in several other biological applications, for which Tom and his collaborators have received substantial funding (BBSRC sLoLa grant for £4 million).

Tom Brown's work is based on the chemical synthesis and biological applications of novel oligonucleotide analogues, a field which he has pioneered (e.g. Nature Protocols 2008, 2, 615-623; Nucleic Acids Res., 2002, 30, e39; JACS 2009, 131, 2831; JACS 2009, 131, 4288; JACS 2011, 133, 279). Another very recent example is a collaboration which has led to the development of a new method for forensic and genetic analysis using SERS detection and electrochemical DNA melting (JACS 2008, 130, 15589; Angew. Chem. 2010, 49, 5917).

Tom's work has produced 300 publications/ patents and 3 successful start-up companies (Oswel, ATDBio, Primer Design). He has has received several awards including 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. Tom is a Fellow of the Royal Society of Edinburgh and a Fellow of the Royal Society of Chemistry. He is a member of the Chemical Biology Interface Division committee of the Royal Society of Chemistry and a member of the editorial board of Chemistry World.

Publications

The University of Southampton's electronic library (e-prints)

Article

Kimber, Scott T., Brown, Tom and Fox, Keith R. (2014) A mutant of uracil DNA glycosylase that distinguishes between cytosine and 5-methylcytosine. PLoS ONE, 9, (4), e95394. (doi:10.1371/journal.pone.0095394).
Birts, Charles N., Sanzone, A. Pia, El-Sagheer, Afaf H., Blaydes, Jeremy P., Brown, Tom and Tavassoli, Ali (2014) Transcription of click-linked DNA in human cells. Angewandte Chemie International Edition in English, 53, (9), 2362-2365. (doi:10.1002/anie.201308691). (PMID:24452865).
Johannsen, Marie W., Gerrard, Simon R., Melvin, Tracy and Brown, Tom (2014) Triplex-mediated analysis of cytosine methylation at CpA sites in DNA. Chemical Communications, 50, (5), 551-553. (doi:10.1039/C3CC45917A).
Riley, Jo-Anne, Brown, Tom, Gale, Nittaya, Herniman, Julie and Langley, G. John (2014) Self-reporting hybridisation assay for miRNA analysis. The Analyst, 139, (5), 1088-1092. (doi:10.1039/C3AN01825C). (PMID:24404560).
Allam, J., Sajjad, M.T., Sutton, R., Litvinenko, K., Wang, Z., Siddique, S., Yang, Q.-H., Loh, W.H. and Brown, T. (2013) Measurement of a reaction-diffusion crossover in exciton-exciton recombination inside carbon nanotubes using femtosecond optical absorption. Physical Review Letters, 111, (19), 1-5. (doi:10.1103/PhysRevLett.111.197401). (PMID:24266488).
Heuer-Jungemann, Amelie, Harimech, Pascal, Brown, Tom and Kanaras, Antonios G. (2013) Gold nanoparticles and fluorescently-labelled DNA as a platform for biological sensing. Nanoscale, 5, (20), 9503-9510. (doi:10.1039/c3nr03707j).
Heuer-Jungemman, Amelie, Kirkwood, Robert, El-Sagheer, Afaf H., Brown, Tom and Kanaras, Antonios G. (2013) Copper-free click chemistry as an emerging tool for the programmed ligation of DNA-functionalised gold nanoparticles. Nanoscale, 5, (16), 7209-7212. (doi:10.1039/C3NR02362A ).
Johnson, Robert P., Gale, Nittaya, Richardson, James A., Brown, Tom and Bartlett, Philip N. (2013) Denaturation of dsDNA immobilised at a negatively charged gold electrode is not caused by electrostatic repulsion. Chemical Science, 4, 1625-1632. (doi:10.1039/c3sc22147d).
Milton, James A., Patole, Samson, Yin, Huabing, Xiao, Qiang, Brown, Tom and Melvin, Tracy (2013) Efficient self-assembly of DNA-functionalized fluorophores and gold nanoparticles with DNA functionalized silicon surfaces: the effect of oligomer spacers. Nucleic Acids Research, 41, (7), e80. (doi:10.1093/nar/gkt031). (PMID:23361467).
Riley, Jo-Anne, Brown, Tom, Gale, Nittaya, Herniman, Julie and Langley, G. John (2012) Self reporting RNA probes as an alternative to cleavable small molecule mass tags. The Analyst, 137, (24), 5817-5822. (doi:10.1039/C2AN36086A ). (PMID:23096125).
Tavassoli, Ali, Brown, Tom, El-Sagheer, Afaf H. and Sanzone, A. Pia (2012) Assessing the biocompatibility of click-linked DNA in Escherichia coli. Nucleic Acids Research, 40, (20), 10567-10575. (doi:10.1093/nar/gks756). (PMID:22904087).
Gerrard, Simon R., Hardiman, Claire, Shelbourne, Montserrat, Nandhakumar, Iris, Nordén, Bengt and Brown, Tom (2012) A new modular approach to nanoassembly: stable and addressable DNA nanoconstructs via orthogonal click chemistries. ACS Nano, 6, (10), 9221-9228. (doi:10.1021/nn3035759).
Johnson, Robert P., Gao, Rachel, Brown, Tom and Bartlett, Philip N. (2012) The effect of base-pair sequence on electrochemically driven denaturation. Bioelectrochemistry, 85, 7-13. (doi:10.1016/j.bioelechem.2011.11.003).
Rusling, David A., Nandhakumar, Iris S., Brown, Tom and Fox, Keith R. (2012) Triplex-directed recognition of a DNA nanostructure assembled by crossover strand exchange. ACS Nano, 6, (4), 3604-3613. (doi:10.1021/nn300718z).
Johnson, Robert P., Richardson, James A., Brown, Tom and Bartlett, Philip N. (2012) A label-free, electrochemical SERS-based assay for detection of DNA hybridization and discrimination of mutations. Journal of the American Chemical Society, 134, (34), 14099-14107. (doi:10.1021/ja304663t).
Johnson, Robert P., Richardson, James , Brown, Tom and Bartlett, Philip N. (2012) Real-time surface-enhanced Raman spectroscopy monitoring of surface pH during electrochemical melting of double-stranded DNA. Langmuir, 28, (12), 5464-5470. (doi:10.1021/la204794g).
Hannestad, Jonas K., Gerrard, Simon R., Brown, Tom and Albinsson, Bo (2011) Self-assembled DNA-based fluorescence waveguide with selectable output. Small, 7, (22), 3178-3185. (doi:10.1002/smll.201101144). (PMID:21901828).
El-Sagheer, Afaf H., Sanzone, A Pia, Gao, Rachel, Tavassoli, Ali and Brown, Tom (2011) Biocompatible artificial DNA linker that is read through by DNA polymerases and is functional in Escherichia coli. Proceedings of the National Academy of Sciences, 108, (28), 11338-11343. (doi:10.1073/pnas.1101519108). (PMID:21709264).
Lou, Chenguang, Xiao, Qiang, Tailor, Radha R., Ben Gaied, Nouha, Gale, Nittaya, Light, Mark E., Fox, Keith R. and Brown, Tom (2011) 2′-Substituted 2-amino-3-methylpyridine ribonucleosides in triplex-forming oligonucleotides: triplex stability is determined by chemical environment. MedChemComm, 2, (6), 550-558. (doi:10.1039/c1md00068c).
Węgrzyn, Ilona, Jeffries, Gavin D.M., Nagel, Birgit, Katterle, Martin, Gerrard, Simon R., Brown, Tom, Orwar, Owe and Jesorka, Aldo (2011) Membrane protrusion coarsening and nanotubulation within giant unilamellar vesicles. Journal of the American Chemical Society, 133, (45), 18046-18049. (doi:10.1021/ja207536a). (PMID:21978148).
Fox, Keith R. and Brown, Tom (2011) Formation of stable DNA triplexes. Biochemical Society Transactions, 39, (2), 629-634. (doi:10.1042/BST0390629).
Ranasinghe, Rohan T. and Brown, Tom (2011) Ultrasensitive fluorescence-based methods for nucleic acid detection: towards amplification-free genetic analysis. Chemical Communications, 47, (13), 3717-3735. (doi:10.1039/c0cc04215c).
Rindermann, Jan J., Akhtman, Yosef, Richardson, James, Brown, Tom and Lagoudakis, Pavlos G. (2011) Gauging the flexibility of fluorescent markers for the interpretation of fluorescence resonance energy transfer. Journal of the American Chemical Society, 133, (2), 279-285. (doi:10.1021/ja105720j).
Gerrard, Simon R., Edrees, Mastoura M., Bouamaied, Imenne, Fox, Keith R. and Brown, Tom (2010) CG base pair recognition within DNA triple helices by modified N-methylpyrrolo-dC nucleosides. Organic & Biomolecular Chemistry, 8, (22), 5087-5096. (doi:10.1039/c0ob00119h). (PMID:20835452).
Lou, Chenguang, Xiao, Qiang, Brennan, Lavinia, Light, Mark E., Vergara-Irigaray, Nuria, Atkinson, Elizabeth M., Holden-Dye, Lindy M.., Fox, Keith R. and Brown, Tom (2010) Synthesis and properties of triplex-forming oligonucleotides containing 2′-O-(2-methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine. Bioorganic & Medicinal Chemistry, 18, (17), 6389-6397. (doi:10.1016/j.bmc.2010.07.005). (PMID:20674370).
Corrigan, Damion, Gale, Nittaya, Brown, Tom and Bartlett, Philip N. (2010) Analysis of short tandem repeats by using SERS monitoring and electrochemical melting. Angewandte Chemie International Edition, 49, (34), 5917-5920. (doi:10.1002/anie.201001389). (PMID:20623816).
El-Sagheer, Afaf H. and Brown, Tom (2010) New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes. Proceedings of the National Academy of Sciences, 107, (35), 15329-15334. (doi:10.1073/pnas.1006447107). (PMID:20713730).
Ball, Rachel J., Green, Philip S., Gale, Nittaya, Langley, G. John and Brown, Tom (2010) Peptide nucleic acid probes with charged photocleavable mass markers: towards PNA-based MALDI-TOF MS genetic analysis. Artificial DNA: PNA & XNA, 1, (1), 27-35. (doi:10.4161/adna.1.1.12199).
El-Sagheer, Afaf H. and Brown, Tom (2010) Click chemistry with DNA. Chemical Society Reviews, 39, (4), 1388-1405. (doi:10.1039/b901971p).
Glynne-Jones, P., Boltryk, R.J., Hill, M., Zhang, F., Dong, L., Wilkinson, J.S., Brown, T., Melvin, T. and Harris, N.R. (2010) Multi-modal particle manipulator to enhance bead-based bioassays. Ultrasonics, 50, (2), 235-239. (doi:10.1016/j.ultras.2009.09.025).
Richardson, James A., Gerowska, Marta, Shelbourne, Montserrat, French, David and Brown, Tom (2010) Six-colour HyBeacon probes for multiplex genetic analysis. ChemBioChem, 11, (18), 2530-2533. (doi:10.1002/cbic.201000623). (PMID:21108272).
Ben Gaied, Nouha, Richardson, James A., Singleton, Daniel G., Zhao, Zhengyun, French, David and Brown, Tom (2010) End-capped HyBeacon probes for the analysis of human genetic polymorphisms related to warfarin metabolism. Organic & Biomolecular Chemistry (doi:10.1039/C001177K).
Rusling, David A., Rachwal, Philip A., Brown, Tom and Fox, Keith R. (2009) The stability of triplex DNA is affected by the stability of the underlying duplex. Biophysical Chemistry, 145, (2-3), 105-110. (doi:10.1016/j.bpc.2009.09.007).
Chernatynskaya, Anna V., Deleeuw, Lynn, Trent, John O., Brown, Tom and Lane, Andrew N. (2009) Structural analysis of the DNA target site and its interaction with Mbp1. Organic & Biomolecular Chemistry, 7, (23), 4981-4991. (doi:10.1039/b912309a).
Mahajan, Sumeet, Richardson, James, Gaied, Nouha Ben, Zhao, Zhengyun, Brown, Tom and Bartlett, Philip N. (2009) The Use of an electroactive marker as a SERS label in an E-melting mutation discrimination assay. Electroanalysis, 21, (20), 2190-2197. (doi:10.1002/elan.200904681).
Ben Gaied, Nouha, Zhao, Zhengyun, Gerrard, Simon R., Fox, Keith R. and Brown, Tom (2009) Potent triple helix stabilization by 5′,3′-modified triplex-forming oligonucleotides. ChemBioChem, 10, (11), 1839-1851. (doi:10.1002/cbic.200900232). (PMID:19554592).
El-Sagheer, Afaf H. and Brown, Tom (2009) Synthesis and polymerase chain reaction amplification of DNA strands containing an unnatural triazole linkage. Journal of the American Chemical Society, 131, (11), 3958-3964. (doi:10.1021/ja8065896).
Börjesson, Karl, Preus, Søren, El-Sagheer, Afaf H., Brown, Tom, Albinsson, Bo and Wilhelmsson, L. Marcus (2009) Nucleic acid base analog fret-pair facilitating detailed structural measurements in nucleic acid containing systems. Journal of the American Chemical Society, 131, (12), 4288-4293. (doi:10.1021/ja806944w).
Rusling, David A., Peng, Guomei, Srinivasan, Natarajan, Fox, Keith R and Brown, Tom (2009) DNA triplex formation with 5-dimethylaminopropargyl deoxyuridine. Nucleic Acids Research, 37, (4), 1288-1296. (doi:10.1093/nar/gkn1060).
Glynne-Jones, Peter, Boltryk, Rosemary J., Hill, Martyn, Zhang, Fan, Dong, Liqin, Wilkinson, James S., Melvin, Tracy, Harris, Nicholas R. and Brown, Tom (2009) Flexible acoustic particle manipulation device with integrated optical waveguide for enhanced microbead assays. Analytical Sciences, 25, (2), 285-291. (doi:10.2116/analsci.25.285).
Sandin, Peter, Tumpane, John, Börjesson, Karl, Wilhelmsson, L. Marcus, Brown, Tom, Nordén, Bengt, Albinsson, Bo and Lincoln, Per (2009) Thermodynamic aspects of DNA nanoconstruct stability and design. Journal of Physical Chemistry C, 113, (15), 5941-5946. (doi:10.1021/jp808239a).
Mahajan, Sumeet, Richardson, James, Ben Gaied, Nouha, Zhao, Zhengyun, Brown, Tom and Bartlett, Philip N. (2009) The use of an electroactive marker as a SERS label in an E-melting mutation discrimination assay. Electroanalysis, 21, (20), 2190-2197. (doi:10.1002/elan.200904681).).
Baldelli Bombelli, Francesca, Betti, Francesca, Gambinossi, Filippo, Caminati, Gabriella, Brown, Tom, Baglioni, Piero and Berti, Debora (2009) Closed nanoconstructs assembled by step-by-step ss-DNA coupling assisted by phospholipid membranes. Soft Matter, 5, (8), 1639-1645. (doi:10.1039/b816716h).
Bombelli, Francesca Baldelli, Gambinossi, Filippo, Lagi, Marco, Berti, Debora, Caminati, Gabriella, Brown, Tom, Sciortino, Francesco, Nordén, Bengt and Baglioni, Piero (2008) DNA closed nanostructures: a structural and Monte Carlo simulation study. Journal of Physical Chemistry B, 112, (48), 15283-15294. (doi:10.1021/jp804544u).
El-Sagheer, Afaf H. and Brown, Tom (2008) Synthesis, serum stability and cell uptake of cyclic and hairpin decoy Oligonucleotides for TCF/LEF and GLI transcription factors. International Journal of Peptide Research and Therapeutics, 14, (4), 367-372. (doi:10.1007/s10989-008-9153-0).
Mahajan, Sumeet, Richardson, James, Brown, Tom and Bartlett, Philip N. (2008) SERS-melting: a new method for discriminating mutations in dna sequences. Journal of the American Chemical Society, 130, (46), 15589-15601. (doi:10.1021/ja805517q).
Stevenson, R., Baxter, H., Aitken, A., Brown, Tom and BAXTER, R. (2008) Binding of 14-3-3 proteins to a single stranded oligodeoxynucleotide aptamer. Bioorganic Chemistry, 36, (5), 215-219. (doi:10.1016/j.bioorg.2007.12.005).
French, D., Howard, R., Gale, Nittaya, Brown, Tom, McDowell, D. and Debenham, P. (2008) Interrogation of short tandem repeats using fluorescent probes and melting curve analysis: A step towards rapid DNA identity screening. Forensic Science International: Genetics, 2, (4), 333-339. (doi:10.1016/j.fsigen.2008.04.007).
Kočalka, Petr, El-Sagheer, Afaf H. and Brown, Tom (2008) Rapid and efficient DNA strand cross-linking by click chemistry. ChemBioChem, 9, (8), 1280-1285. (doi:10.1002/cbic.200800006). (PMID:18418819).
Yang, Quan-Hong, Wang, Qi, Gale, Nittaya, Oton, Claudio J., Cui, Lan, Nandhakumar, Iris S., Zhu, Zhenping, Tang, Zhiyuan, Brown, Tom and Loh, Wei H. (2008) Loosening the DNA wrapping around single-walled carbon nanotubes by increasing the strand length. Nanotechnology, 20, (19), 1-6. (doi:10.1088/0957-4484/20/19/195603). (PMID:19420642).
El-Sagheer, Afaf H., Kumar, Ravindra, Findlow, Stuart C. , Werner, Joern M., Lane, Andrew N. and Brown, Tom (2008) A very stable cyclic DNA miniduplex with just two base pairs. ChemBioChem, 9, (1), 50-52. (doi:10.1002/cbic.200700538). (PMID:18058775).
Sandin, Peter, Borjesson, Karl, Li, Hong, Martensson, Jerker, Brown, Tom, Wilhelmsson, L. Marcus and Albinsson, Bo (2008) Characterization and use of an unprecedentedly bright and structurally non-perturbing fluorescent DNA base analogue. Nucleic Acids Research, 36, (1), 157-167. (doi:10.1093/nar/gkm1006). (PMID:18003656).
Erkan, Yavuz, Halma, Kiona, Czolkos, Ilja, Jesorka, Aldo, Dommersnes, Paul, Kumar, Ravindra, Brown, Tom and Orwar, Owe (2008) Controlled release of Chol-TEG-DNA from Nano- and micropatterned SU-8 surfaces by a spreading lipid film. Nano Letters, 8, (1), 227. (doi:10.1021/nl0725087).
Rusling, David A., Broughton-Head, Victoria J., Tuck, Alex, Khairallah, Hannah, Osborne, Sadie D., Brown, Tom and Fox, Keith R. (2008) Kinetic studies on the formation of DNA triplexes containing the nucleoside analogue 2′-O-(2-aminoethyl)-5-(3-amino-1-propynyl)uridine. Organic & Biomolecular Chemistry, 6, (1), 122-129. (doi:10.1039/b713088k). (PMID:18075656).
Fox, Keith R., Rusling, David A., Broughton-Head, Victoria J. and Brown, Tom (2008) Towards the targeted modulation of gene expression by modified triplex-forming oligonucleotides. Current Chemical Biology, 2, (1), 1-10. (doi:10.2174/187231308783334135).
Nordell, Pär, Westerlund, Fredrik, Reymer, Anna, El-Sagheer, Afaf H., Brown, Tom, Nordén, Bengt and Lincoln, Per (2008) DNA polymorphism as an origin of adenine-thymine tract length-dependent threading intercalation rate. Journal of the American Chemical Society, 130, (44), 14651-14658. (doi:10.1021/ja804427q).
Banchelli, Martina, Betti, Francesca, Berti, Debora, Caminati, Gabriella, Bombelli, Francesca Baldelli, Brown, Tom, Wilhelmsson, L. Marcus, Nordén, Bengt and Baglioni, P. (2008) Phospholipid membranes decorated by cholesterol-based oligonucleotides as soft hybrid nanostructures. Journal of Physical Chemistry B, 112, (35), 10942-10952. (doi:10.1021/jp802415t).
Yang, Quan-Hong, Gale, Nittaya, Oton, Claudio J, Li, Hong, Nandhakumar, Iris S., Tang, Zhi-Yuan, Brown, Tom and Loh, Wei H. (2007) Deuterated water as super solvent for short carbon nanotubes wrapped by DNA. Carbon, 45, (13), 2701-2073. (doi:10.1016/j.carbon.2007.08.014).
Yang, Quan-Hong, Gale, Nittaya, Oton, Claudio J., Li, Feng, Vaughan, Alun, Saito, Riichiro, Nandhakumar, Iris S., Tang, Zhi Yuan, Cheng, Hui-Ming, Brown, Tom and Loh, Wei (2007) Raman probe for selective-wrapping of single-walled carbon nanotubes by DNA. Nanotechnology, 18, (40), 1-5. (doi:10.1088/0957-4484/18/40/405706).
Gerrard, Simon R., Natarajan, Srinivasan, Fox, Keith R. and Brown, Tom (2007) CG base pair recognition within DNA triple helices using N-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleoside analogues. Nucleosides, Nucleotides and Nucleic Acids, 26, (10-12), 1363-1367. (doi:10.1080/15257770701533958).
Brennan, Lavinia, Peng, Guomei, Srinivasan, Natarajan, Fox, Keith R. and Brown, Tom (2007) 2 '-O-dimethylaminoethoxyuridine and 5-dimethylaminopropargyl deoxyuridine for at base pair recognition in triple helices. Nucleosides, Nucleotides and Nucleic Acids, 26, (10-12), 1283-1286. (doi:10.1080/15257770701530525).
Zhao, Zhengyun, Peng, Guomei, Michels, Jan, Fox, Keith R. and Brown, Tom (2007) Synthesis of anthraquinone oligonucleotides for triplex stabilization. Nucleosides, Nucleotides and Nucleic Acids, 26, (8 & 9), 921-925. (doi:10.1080/15257770701506491).
Li, Hong, Broughton-Head, Victoria J., Fox, Keith R. and Brown, Tom (2007) Photoinduced crosslinking of double-helical DNA by psoralen covalently linked to a triple helix-forming oligonucleotide under near-physiological conditions. Nucleosides, Nucleotides and Nucleic Acids, 26, (8 & 9), 1005-1009. (doi:10.1080/15257770701508554).
Durand, Adeline and Brown, Tom (2007) Synthesis and properties of oligonucleotides containing a cholesterol thymidine monomer. Nucleosides, Nucleotides and Nucleic Acids, 26, (6 & 7), 785-794. (doi:10.1080/15257770701501534).
Tumpane, John, Sandin, Peter, Kumar, Ravindra, Powers, Vicki E.C., Lundberg, Erik P., Gale, Nittaya, Baglioni, Piero, Lehn, Jean-Marie, Albinsson, Bo, Lincoln, Per, Wilhelmsson, L. Marcus , Brown, Tom and Nordén, Bengt (2007) Addressable high-information-density DNA nanostructures. Chemical Physics Letters, 440, (1-3), 125-129. (doi:10.1016/j.cplett.2007.04.018).
Kumar, Ravindra, El-Sagheer, Afaf, Tumpane, John, Lincoln, Per, Wilhelmsson, L. Marcus and Brown, Tom (2007) Template-directed oligonucleotide strand ligation, covalent intramolecular DNA circularization and catenation using click chemistry. Journal of the American Chemical Society, 129, (21), 6859-6864. (doi:10.1021/ja070273v).
Rachwal, Phillip A., Brown, Tom and Fox, Keith R. (2007) Sequence effects of single base loops in intramolecular quadruplex DNA. FEBS Letters, 581, (8), 1657-1660. (doi:10.1016/j.febslet.2007.03.040).
Rachwal, Philip A., Brown, Tom and Fox, Keith R. (2007) Effect of G-tract length on the topology and stability of intramolecular DNA quadruplexes. Biochemistry, 46, (11), 3036-3044. (doi:10.1021/bi062118j).
Tumpane, J., Kumar, R., Lundberg, E.P., Sandin, P., Gale, N., Nandhakumar, I.S., Albinsson, B., Lincoln, P., Wilhelmsson, L.M., Brown, T. and Norden, B. (2007) Triplex addressability as a basis for functional DNA nanostructures. Nano Letters, 7, (12), 3832-3839. (doi:10.1021/nl072512i).
Hammond, N., Koumi, P., Langley, G.J., Lowe, A. and Brown, T. (2007) Rapid mass spectrometric identification of human genomic polymorphisms using multiplexed photocleavable mass-tagged probes and solid phase capture. Organic & Biomolecular Chemistry, 5, (12), 1878-1885. (doi:10.1039/b704587e).
Bunyan, D.J., Skinner, A.C., Ashton, E.J., Sillibourne, J., Brown, T., Collins, A.L., Cross, N.C.P., Harvey, J.F. and Robinson, D.O. (2007) Simultaneous MLPA-based multiplex point mutation and deletion analysis of the dystrophin gene. Molecular Biotechnology, 35, (2), 135-140. (doi:10.1007/s12033-007-9014-7).
Sandin, P., Lincoln, P., Brown, T. and Wilhelmsson, L.M. (2007) Synthesis and oligonucleotide incorporation of fluorescent cytosine analogue tC: a promising nucleic acid probe. Nature Protocols, 2, (3), 615-623. (doi:10.1038/nprot.2007.80).
Li, Hong, Broughton-Head, Victoria J., Peng, Guomei, Powers, Vicki E.C., Ovens, Matthew J., Fox, Keith R.. and Brown, Tom (2006) Triplex staples: DNA double-strand cross-linking at internal and terminal sites using psoralen-containing triplex-forming oligonucleotides. Bioconjugate Chemistry, 17, (6), 1561-1567. (doi:10.1021/bc0601875).
Rusling, David A., Brown, Tom and Fox, Keith R. (2006) DNA triple-helix formation at target sites containing duplex mismatches. Biophysical Chemistry, 123, (2-3), 134-140. (doi:10.1016/j.bpc.2006.04.016).
Hampshire, Andrew J., Khairallah, Hannah, Khalaf, Abedawn I., Ebrahimabadi, Abdolrasoul H., Waigh, Roger D., Suckling, Colin J., Brown, Tom and Fox, Keith R. (2006) DNA sequence recognition by an imidazole-containing isopropyl-substituted thiazole polyamide (thiazotropsin B). Bioorganic & Medicinal Chemistry Letters, 16, (13), 3469-3474. (doi:10.1016/j.bmcl.2006.04.007).
Brown, Nicholas M., Rachwal, Phillip A., Brown, Tom and Fox, Keith R. (2005) Exceptionally slow kinetics of the intramolecular quadruplex formed by the Oxytricha telomeric repeat. Organic & Biomolecular Chemistry, 3, (22), 4153-4157. (doi:10.1039/b511706b). (PMID:16267597).
Fox, Keith R. and Brown, Tom (2005) An extra dimension in nucleic acid sequence recognition. Quarterly Reviews of Biophysics, 38, (4), 311-320. (doi:10.1017/S0033583506004197).
Rusling, David A., Powers, Vicki E.C., Ranasinghe, Rohan T., Wang, Yang, Osborne, Sadie D., Brown, Tom and Fox, Keith R. (2005) Four base recognition by triplex-forming oligonucleotides at physiological pH. Nucleic Acids Research, 33, (9), 3025-3032. (doi:10.1093/nar/gki625).
Dyadyusha, L., Yin, H., Jaiswal, S., Brown, T., Baumberg, J.J., Booy, F.P. and Melvin, T. (2005) Quenching of CdSe quantum dot emission, a new approach for biosensing. Chemical Communications, 25, 3201-3203. (doi:10.1039/b500664c).
Ranasinghe, Rohan T., Rusling, David A., Powers, Vicki E.C., Fox, Keith R. and Brown, Tom (2005) Recognition of CG inversions in DNA triple helices by methylated 3H-pyrrolo [2,3-d] pyrimidin-2(7H)-one nucleoside analogues. Chemical Communications, 20, 2555-2557. (doi:10.1039/b502325d).
Wang, Yang, Rusling, David A., Powers, Vicki E.C., Lack, Oliver, Osborne, Sadie D., Fox, Keith R. and Brown, Tom (2005) Stable recognition of TA interruptions by triplex forming oligonucleotides containing a novel nucleoside. Biochemistry, 44, (15), 5884-5892. (doi:10.1021/bi050013v).
May, Jonathan P., Brown, Lynda J., van Delft, Ian, Thelwell, Nicola, Harley, Kate and Brown, Tom (2005) Synthesis and evaluation of a new non-fluorescent quencher in fluorogenic oligonucleotide probes for real-time PCR. Organic & Biomolecular Chemistry, 3, (14), 2534-2542. (doi:10.1039/B504759E).
James, P.L., Le Strat, L., Ellervik, U., Bratwall, C., Norden, B., Brown, T. and Fox, K.R. (2004) Effects of a hairpin polyamide on DNA melting: comparison with distamycin and Hoechst 33258. Biophysical Chemistry, 111, (3), 205-212.
Yin, H.B., Brown, T., Wilkinson, J.S., Eason, R.W. and Melvin, T. (2004) Submicron patterning of DNA oligonucleotides on silicon. Nucleic Acids Research, 32, (14), e118-[7pp]. (doi:10.1093/nar/gnh113).
Yin, H.B., Brown, T., Greef, R., Wilkinson, J.S. and Melvin, T. (2004) Chemical modification and micropatterning of Si(100) with oligonucleotides. Microelectronic Engineering, 73-73, 830-836. (doi:10.1016/j.mee.2004.03.060).
James, Peter L., Merkina, Elena E., Khalaf, Abedawn I., Suckling, Colin J., Waigh, Roger D., Brown, Tom and Fox, Keith R. (2004) DNA sequence recognition by an isopropyl substituted thiazole polyamide. Nucleic Acids Research, 32, (11), 3410-3417. (doi: 10.1093/nar/gkh666).
Osborne, Sadie D., Powers, Vicki E.C., Rusling, David A., Lack, Oliver, Fox, Keith R. and Brown, Tom (2004) Selectivity and affinity of triplex-forming oligonucleotides containing 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine for recognizing AT base pairs in duplex DNA. Nucleic Acids Research, 32, (15), 4439-4447. (doi:10.1093/nar/gkh776).
Engman, K. Cecilia, Sandin, Peter, Osborne, Sadie, Brown, Tom, Billeter, Martin, Lincoln, Per, Nordén, Bengt, Albinsson, Bo and Wilhelmsson, L. Marcus (2004) DNA adopts normal B-form upon incorporation of highly fluorescent DNA base analogue tC: NMR structure and UV-Vis spectroscopy characterization. Nucleic Acids Research, 32, (17), 5087-5095. (doi: 10.1093/nar/gkh844).
Booth, J., Cummins, W. J. and Brown, T. (2004) An analogue of adenine that forms an 'A : T' base pair of comparable stability to G : C. Chemical Communications, (19), 2208-2209. (doi: 10.1039/b409155h).
Bunyan, David J., Brown, T., Wycherley, R., Score, J. C., Harvey, J. F. and Cross, N. C. P. (2004) MLPA-based point mutation analysis of the FBN1 gene in Marfan syndrome. Journal of Medical Genetics, 41, (S75), 1-1.
Keppler, Melanie D., James, Peter L., Neidle, Stephen, Brown, Tom and Fox, Keith R. (2003) DNA sequence specificity of triplex-binding ligands. European Journal of Biochemistry, 270, (24), 4982-4992. (doi: 10.1046/j.1432-1033.2003.03901.x).
James, Peter L., Brown, Tom and Fox, Keith R. (2003) Thermodynamic and kinetic stability of intermolecular triple helices containing different proportions of C+·GC and T·AT triplets. Nucleic Acids Research, 31, (19), 5598-5606. (doi:10.1093/nar/gkg782).
Gyi, Jeffrey I., Gao, Daquan, Conn, Graeme L., Trent, John O., Brown, Tom and Lane, Andrew N. (2003) The solution structure of a DNA·RNA duplex containing 5-propynyl U and C; comparison with 5-Me modifications. Nucleic Acids Research, 31, (10), 2683-2693. (doi: 10.1093/nar/gkg356).
Brown, J., Brown, T. and Fox, K.R. (2003) Cleavage of fragments containing DNA mismatches by enzymic and chemical probes. Biochemical Journal, 371, (3), 697-708. (doi:10.1042/BJ20021847).
Bunting, Karen A., Roe, S. Mark, Headley, Anthony, Brown, Tom, Savva, Renos and Pearl, Laurence H. (2003) Crystal structure of the Escherichia coli dcm very-short-patch DNA repair endonuclease bound to its reaction product-site in a DNA superhelix. Nucleic Acids Research, 31, (6), 1633-1639. (doi:10.1093/nar/gkg273).
McKeen, Catherine M., Brown, Lynda J., Nicol, Jamie T.G., Mellor, John M. and Brown, Tom (2003) Synthesis of fluorophore and quencher monomers for use in Scorpion primers and nucleic acid structural probes. Organic & Biomolecular Chemistry, 1, (13), 2267-2275. (doi:10.1039/b301859h). (PMID:12945696).
Dobson, N., McDowell, D.G., French, D.J., Brown, L.J., Mellor, J.M. and Brown, T. (2003) Synthesis of HyBeacons and dual-labelled probes containing 2'- fluorescent groups for use in genetic analysis. Chemical Communications, (11), 1234-1235. (doi:10.1039/b302855k).
Anderson, Emma, Brown, Tom and Picken, Douglas (2003) Novel photocleavable universal support for oligonucleotide synthesis. Nucleosides, Nucleotides & Nucleic Acids, 22, (5-8), 1403-1406.
May, J.P., Brown, L.J., Rudloff, I. and Brown, T. (2003) A new dark quencher for use in genetic analysis. Chemical Communications, (8), 970-971. (doi:10.1039/b300934c).
Pinheiro, Philip, Scarlett, Garry, Rodger, Alison, Rodger, P. Mark, Murray, Anna, Brown, Tom, Newbury, Sarah F. and McClellan, James A. (2002) Structures of CUG repeats in RNA: potential implications for human genetic diseases. Journal of Biological Chemistry, 277, (38), 35183-35190. (doi:10.1074/jbc.M202235200).
Sollogoub, Matthieu, Darby, Richard A.J., Cuenoud, Bernard, Brown, Tom and Fox, Keith R. (2002) Stable DNA triple helix formation using oligonucleotides containing 2'-aminoethoxy,5-propargylamino-U. Biochemistry - US, 41, (23), 7224-7231. (doi: 10.1021/bi020164n).
Darby, R.A.J., Sollogoub, M., McKeen, M., Brown, Lynda J., Risitano, A., Brown, N., Barton, C., Brown, Tom and Fox, K.R. (2002) High throughput measurement of duplex, triplex and quadruplex melting curves using molecular beacons and a LightCycler. Nucleic Acids Research, 30, (9), e39-[9pp]. (doi:10.1093/nar/30.9.e39). (PMID:11972354).
Sollogoub, M., Fox, K. R., Powers, V. E. C. and Brown, T. (2002) First synthesis of 1-deazacytidine, the C-nucleoside analogue of cytidine. Tetrahedron Letters, 43, (17), 3121-3123. (doi:10.1016/S0040-4039(02)00481-1).
Solinas, A., Thelwell, N. and Brown, T. (2002) Intramolecular TaqMan probes for genetic analysis. Chemical Communications, (19), 2272-2273. (doi: 10.1039/b207254h).
French, D.J., Archard, C.L., Brown, T. and McDowell, D.G. (2001) HyBeacon (TM) probes: a new tool for DNA sequence detection and allele discrimination. Molecular and Cellular Probes, 15, (6), 363-374. (doi: 10.1006/mcpr.2001.0384).
Solinas, Antonio, Brown, Lynda J., McKeen, Catherine, Mellor, John M., Nicol, Jamie T.G., Thelwell, Nicky and Brown, Tom (2001) Duplex Scorpion primers in SNP analysis and FRET applications. Nucleic Acids Research, 29, (20), 1-9. (doi:10.1093/nar/29.20.e96). (PMID:11600715).
Hart, Keith W., Williams, O. Martin, Thelwell, Nicola, Fiander, Alison N., Brown, Tom, Borysiewicz, Lesek K. and Gelder, Colin M. (2001) Novel method for detection, typing, and quantification of human papillomaviruses in clinical samples. Journal of Clinical Microbiology, 39, (9), 3204-3212. (doi: 10.1128/JCM.39.9.3204-3212.2001).
Ranasinghe, R.T., Brown, L.J. and Brown, T. (2001) Linear fluorescent oligonucleotide probes with an acridine quencher generate a signal upon hybridisation. Chemical Communications, (16), 1480-1481. (doi:10.1039/b104421b).
Brown, James, Brown, Tom and Fox, Keith R. (2001) Affinity of mismatch-binding protein MutS for heteroduplexes containing different mismatches. Biochemical Journal, 354, (3), 627-633.
Sollogoub, M., Dominguez, B., Fox, K.R. and Brown, T. (2000) Synthesis of a novel bis-amino-modified thymidine monomer for use in DNA triplex stabilisation. Chemical Communications, 23, 2315-2316. (doi:10.1039/b006268p).
Fox, K.R., Allinson, S.L., Sahagun-Krause, H. and Brown, T. (2000) Recognition of GT mismatches by Vsr mismatch endonuclease. Nucleic Acids Research, 28, (13), 2535-2540. (doi:10.1093/nar/28.13.2535).
Brown, Lynda J., Cummins, Jon, Hamilton, Alan and Brown, Tom (2000) Molecular beacons attached to glass beads fluoresce upon hybridisation to target DNA. Chemical Communications, 7, 621-622. (doi:10.1039/b000389l).

Book

Fox, Keith R. and Brown, Tom (eds.) (2012) DNA conjugates and sensors, London, GB, Royal Society of Chemistry, 316pp. (Biomolecular Science Series).

Book Section

Rusling, David A., Brown, Tom and Fox, Keith R. (2006) DNA recognition by triple helix formation. In, Waring, M.J. (ed.) Sequence-specific DNA Binding Agents. London, GB, Royal Society of Chemistry, 1-28. (doi:10.1039/9781847555304-00001).
Yin, Huabing B., Brown, Tom, Greef, Robert, Mailis, Sakellaris, Eason, Rob W., Wilkinson, James S. and Melvin, Tracy (2004) Photo-patterning of DNA oligonucleotides on silicon surfaces with micron-scale dimensions. In, Faupel, Michel D. and Meyrueis, Patrick (eds.) Biophotonics New Frontier: from Genome to Proteome. Biophotonics New Frontier: From Genome to Proteome Bellingham, USA, International Society for Optical Engineering, 1-8. (Proceedings of SPIE, 5461). (doi:10.1117/12.545736).
May, J.P., Brown, L.J. and Brown, T. (2003) Synthesis of a novel dark quencher for use with long wavelength dyes in oligonucleotide probes. In, Epton, Roger (ed.) Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries, 2002: Peptides, Proteins and Nucleic Acids: Small Molecule organic Chemical Diversity: Collected Papers, Seventh International Symposium, Southampton, UK. Birmingham, GB, Mayflower Worldwide, 231-234.
Ranasinghe, R.T., Brown, L.J. and Brown, T. (2003) A novel, linear dual-labelled fluorescent probe for nucleic acid sequence analysis. In, Epton, Roger (ed.) Innovation and Perspectives in Solid Phase Synthesis & Combinatorial Libraries, 2002: Peptides, Proteins and Nucleic Acids: Small Molecule organic Chemical Diversity: Collected Papers, Seventh International Symposium, Southampton, UK. Birmingham, GB, Mayflower Worldwide, 253-256.

Conference or Workshop Item

Glynne-Jones, P., Boltryk, R.J., Hill, M., Zhang, F., Dong, L., Wilkinson, J.S., Brown, T., Melvin, T. and Harris, N.R. (2009) Multi-modal particle manipulator to enhance bead-based bioassays. In, International Congress on Ultrasonics, Santiago, CL, 11 - 17 Jan 2009.
Yin, H.B., Brown, T., Wilkinson, J.S., Eason, R.W. and Melvin, T. (2005) Photonic generation of DNA micropatterns for haplotype analysis. In, BioScience 2005, Glasgow, UK, Jul 2005.

Patent

Brown, L.J. and Brown, T. (Patent Holders) (2001) Intercalated quenchers (acridine). Dual-labelled probes. GB0111833.0.
Brown, L.J., May, J.P. and Brown, T. (Patent Holders) (2001) Dark quencher (non-fluorescent absorbing labels). Novel fluorescence-absorbing compounds. GB0121089.7.
 

Research

Research Interests

My research is interdisciplinary, focusing on nucleic acid chemistry and its applications in other fields including DNA diagnostics, forensic science and nanotechnology. In the early part of my academic career I used NMR and X-ray crystallography to study the properties of base pair mismatches in DNA and their implications for DNA repair. Examples of this research are the elucidation of the structures of DNA duplexes containing G.T (Nature 1985, 315, 604) and A.C mispairs (Nature 1986, 320, 552). This approach led us to determine the molecular basis of the mutagenic effect of a number of chemical lesions in DNA, for example O6-methyl guanine (Proc. Natl. Acad. Sci. USA 1990, 87, 9573). This was the first time that the structural basis of a mutation caused by chemical damage to DNA had been defined at the molecular level. Our studies also highlighted the fact that mispaired bases form distinct structures and cause minimal distortion to the overall conformation of the DNA duplex. Therefore enzymatic recognition of modified base pairs in living systems must depend upon subtle differences. To confirm this we investigated the origin of the recognition of mismatched and mutagenic bases by DNA repair enzymes. An example of this is our collaboration with Laurence Pearl to elucidate the structural basis of specific base-excision repair by uracil-DNA glycosylase (UDGase) and MUG (Nature 1995, 373, 487, and Nature Structural Biology 1998, 5, 697). These essential enzymes reverse the damage that is caused to DNA by oxidation of cytosine bases, recognizing the absence of a single methyl group to initiate excision-repair. UDGase is of interest as a target for antiviral therapy.

The expertise that we gained from these fundamental studies on DNA base pairing was then used in the emerging field of molecular genetics to develop new methods of mutation analysis.  In collaboration with AstraZeneca we invented a novel fluorescence-based real-time PCR method for the identification of mutations and single nucleotide polymorphisms (SNPs) in the human genome. This was one of the first successful technologies for rapid mutation detection and was patented, published in Nature Biotechnology (1999, 17, 804) and marketed as “Scorpion Primers” by a spin-out from AstraZeneca (DxS Genotyping Ltd). I am also co-inventor of “HyBeacons”, novel fluorogenic probes that utilises DNA melting temperature as a means of identifying mutations. HyBeacons, the result of a collaboration with the Laboratory of the Government Chemist, have recently been licensed to an International Biotech company. They can be used for the rapid diagnosis of bacterial infections and genetically-related diseases, and are also being developed by us for Forensic applications (New Scientist Jan 14th 2006). We recently demonstrated that such methodology has potential for rapid human identification at crime scenes and in custody suites, with clear implications for crime detection and related applications (Forensic Sci. Int. Genetics. 2008, 2, 333, Org. Biomol. Chem. 2008, 6, 4553). Our work on genetic and biophysical analysis of DNA is based on the synthesis of novel fluorescent oligonucleotides, a field in which we have a strong background (e.g. Nature Protocols 2008, 2, 615-623, and Nucleic Acids Res., 2002, 30, e39). In the field of DNA sequence analysis a collaboration with Philip Bartlett in Southampton recently led to a new method for identifying mutations in the human genome by a novel combination of SERS detection and electrochemical DNA melting (J. Am. Chem. Soc. 2008, 130, 15589). My work combines fundamental studies with applications, and have always had a strong interest in taking ideas from the research laboratory and turning them into useful tools for other scientists. I was the Founder of Oswel Research Products, the first UK supplier of high quality oligonucleotides and analogues which provided an essential service to chemists and biologists for many years. In Oswel we were able to synthesise oligonucleotide analogues that were not available from any other supplier. We had a long-standing relationship with the UK Forensic Science Service in their work on the National DNA database. Recently I have co-founded two other start-ups, ATDBio (on the Oswel model) and Primer Design. I also consult for several Biotechnology companies.

I am interested in the use of modified oligonucleotides as potential therapeutic agents and in this context we are trying to develop methods of reversing the mutations that give rise to genetic diseases. The basic idea is to initiate DNA repair by the formation of triple helices at the site of the mutation. Triplex forming oligonucleotides (TFO’s) have wider applications in molecular genetics, diagnostics, therapeutics and nanotechnology and for this work we have developed a set of four base analogues that, when incorporated into TFOs, are able to recognize mixed sequence DNA with high specificity. This was the first example of full sequence recognition of a DNA in the major groove (Nucleic Acids Res. 2005, 33, 3025). This work is a collaboration with Keith Fox in Biological Sciences in Southampton. My research has very recently moved in a new direction. We are using the copper-catalysed alkyne-azide coupling reaction to synthesise large covalently closed cyclic DNA structures (DNA catenanes) for use in biological applications and as scaffolds in nanotechnology. Our first paper in this field was one of the most cited JACS papers in 2007 (J. Amer. Chem. Soc. 129, 6859), and two other publications (ChemBioChem 2008, 9, 50, ChemBioChem 2008, 9, 1280) were amongst the most accessed papers when they appeared on the ChemBioChem web site. A recent collaboration with Bengt Norden’s group in Gothenburg involved this DNA click chemistry to elucidate the binding mechanism of a novel threading DNA intercalator (J. Am. Chem. Soc. 2008, 130, 14651). We have developed this chemistry further to synthesise DNA templates containing modified backbones which can be copied by polymerases during PCR. This discovery (J. Am. Chem. Soc. in press.) promises to open up a new field. With careful design it might be possible to use such methodology to synthesise functional DNA strands greater than 1000 bases in length entirely by chemical methods, an order of magnitude longer than is currently achievable. If the aim of this research is achieved it will be an important contribution to the new discipline of Synthetic Biology. A further collaboration with the Norden group led to the synthesis of addressable high-information-density DNA nanostructures (Chem. Phys. Lett. 2007, 440, 125). These constructs constitute scaffolds on which molecules can be attached at pre-determined locations with nanometre precision so that they can communicate in a controlled manner by energy or electron transfer.

My research spans several fields and a high proportion of my publications appear in biology, biochemistry and nanotechnology journals. Our endeavours have given rise to numerous new analytical techniques that are now used in the real world, particularly in the field of genomics and diagnostics. I have received recognition intenationally, for example I was one of the selected speakers at a Nobel Workshop addressing the frontiers of proteins and nucleic acids, another speaker being Andy Fire who was awarded the Nobel Prize for his discovery of RNAi, and in 2008 I gave a plenary talk, together with the Chemistry Nobel Laureates Barry Sharpless, Ryoji Noyori and Richard Schrock, at the Molecular Frontiers Symposium in Singapore.

 

Research project affiliated with Biological Sciences:  DNA quadruplexes and their interaction with ligands

Primary research group:  Molecular Diagnostics and Therapeutics

Research projects

Modifying nucleic acid nanostructures by triplex formation

We are exploiting the formation of DNA triplexes as a means for generating new DNA nanostructures.

Modifying Uracil DNA Glycosylase

We are generating mutants of this DNA repair enzyme, which have altered recognition properties, and are using these as tools in biotechnological applications.

Extending the boundaries of nucleic acid chemistry

We are part of this BBSRC-funded sLoLa project, led by Prof Tom Brown (Chemistry), and are using click-chemistry to generate unusual DNA structures and examine their biological properties.

Contact

Professor Tom Brown
Chemistry
University of Southampton
Highfield
Southampton
SO17 1BJ

Room Number: 30/5037

Telephone: (023) 8059 2974
Facsimile: (023) 8059 2991
Email: tb2@soton.ac.uk