Professor Mark Fisher's research interests involve DNA topoisomerases and their interactions with anti-cancer and antibacterial drugs.
Topoisomerases are essential enzymes that control chromosomal DNA supercoiling and unlink catenated chromosomes prior to cell division.
His key research interests include molecular biology, microbiology, bacterial genetics, protein expression and structural biology.
Following his postdoctoral work that defined the double-strand break mechanism of E. coli gyrase, his team has sought to address how topoisomerases act as molecular machines and interact with drugs. They have characterised the human topoisomerase II alpha and beta isoforms and Candida topo II using yeast systems to dissect function and anticancer drug binding. They were one of the first groups to focus specifically on gyrase and topo IV as drug targets in medically-important pathogens such as Streptococcus, Staphylococcus and M. tuberculosis.
Recently, in collaboration with Dr Mark Sanderson at King’s College London, the group solved the crystal structures of S. pneumoniae topo IV in complex with DNA and antibacterial quinolones and quinazolinediones. This important advance should aid discovery of new antibiotics that circumvent resistance. PhD and postdoctoral enquiries welcome.
Laponogov I, Pan X-S, Veselkov DA, McAuley K, Fisher LM and Sanderson MR. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS ONE 5, e11338 (2010).
Laponogov I, Sohi MK, Veselkov DA, Pan X-S, Sawhney R, Thompson AW, McAuley K, Fisher LM and Sanderson MR. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat Struct Mol Biol 16, 667-669 (2009)
Pan XS, Gould KA and Fisher LM. Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV. Antimicrob Agents Chemother 53, 3822-3831 (2009)
Cambau E, Matrat S, Pan XS, Roth Di Bettoni R, Corbel C, Aubry A, Lascols C, Driot J-Y and Fisher LM. Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and E. coli. J Antimicrob Chemother, 63, 443-50 (2009).
Pan XS, Dias M, Palumbo M and Fisher LM. Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage. Nucleic Acids Res 36, 5516-29 (2008).
Laponogov I, Veselkov DA, Sohi MK, Pan, X-S, Achari A, Yang C, Ferrara JD, Fisher LM and Sanderson MR. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target. PLoS ONE 2, e301 (2007).
Professor Emmanuelle Cambau, University of Paris, France.
Dr Alexandra Aubry and Prof Vincent Jarlier, University of Paris, France.
Professor Manlio Palumbo, University of Padua, Italy.
Dr Mark Sanderson, King’s College London, UK.
Professor Fisher has been funded by the Biotechnology and Biological Sciences Research Council.