Alan Fairlamb

Professor Alan Fairlamb

Position: Professor of Biochemistry, Wellcome Principal Research Fellow and Head of the Division of Biological Chemistry and Drug Discovery
Division: Biological Chemistry and Drug Discovery
Address: College of Life Sciences, University of Dundee, Dundee
Telephone: +44 1382 385155, int ext. 85155
Fax: +44 1382 385542
Email: a.h.fairlamb@dundee.ac.uk
Website: Fairlamb Lab Group

Research

Biochemical Drug Targets in Parasites

Better, safer and affordable drugs are needed for neglected tropical parasitic diseases. My research interests cover the early aspects of the drug discovery process, including discovery of novel drug targets, their mechanistic and structural  characterisation and their validation using genetic and chemical approaches.

Drugs acting on the trypanothione pathway and trypanothione enzyme structures My studies on the modes of drug action and the mechanisms by which parasites acquire resistance to drugs such as the arsenical, melarsoprol, resulted in the discovery of trypanothione, a metabolite unique to trypanosomatid parasites responsible for human African trypanosomiasis, Chagas' disease and leishmaniasis. Trypanothione and its ancillary enzymes are attractive drug targets,  because they play a central role in thiol-redox homeostasis, in defence against chemical and oxidative stress, in drug resistance to antimonials and in metabolism of deoxyribonucleotides and methylglyoxal.

I collaborate closely with other members of the Drug Discovery Unit on assay development and HTS (Julie Frearson) and medicinal chemistry (Paul Wyattand Ian Gilbert).

Publications

1. Berriman, M., et al. (2005) The genome of the African trypanosome, Trypanosoma brucei. Science, 309, 416-422.
2. Sienkiewicz, N., et al. (2008) Chemical and genetic validation of dihydrofolate reductase-thymidylate synthase as a drug target in African trypanosomes. Molecular Microbiology, 69: 520-533
3. Oza, S.L., Chen, S., Wyllie, S., Coward, J.K. and Fairlamb, A.H. (2008) ATP-dependent ligases in trypanothione biosynthesis: Kinetics of catalysis and inhibition by phosphinic acid pseudopeptides. FEBS Journal, 275: 5408-21
4. Patterson, S., et al. (2009) Synthesis and evaluation of 1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase. ChemMedChem, 4: 1341-1353
5. Wyllie, S., et al. (2009) Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods. Molecular Microbiology, 74: 529-540

Awards

  • Fellow of the Society of Biology (2011)
  • Commander of the Order of the British Empire (CBE) (2006)
  • Kitasato Microbial Chemistry Medal (2005)
  • Fellow of the Academy of Medical Sciences (2005)
  • Fellow of the Royal Society of Edinburgh (2001)
  • The C.A. Wright Memorial Medal, British Society for Parasitology (1990)
  • Fellow of the Linnean Society (1989)