Alan Fairlamb

Alan Hutchinson Fairlamb, CBE, FRSE, FLS, FMedSci, FRSB (born 30 April 1947, Newcastle upon Tyne, England) is a Wellcome Trust Principal Research Fellow and Professor of Biochemistry in the Division of Biological Chemistry and Drug Discovery at the School of Life Sciences, University of Dundee, Scotland. From 2006-2011 he was a member of the Scientific and Technical Advisory Committee of the Special Programme for Research and Training in Tropical Diseases (TDR) -- an independent global programme of scientific collaboration co-sponsored by UNICEF, UNDP, the World Bank and WHO. Currently he is a member of the governing board of the Tres Cantos Open Lab Foundation, whose aim is to accelerate the discovery and development of medicines to tackle diseases of the developing world in an open collaborative manner.

Trypanothione. The glutathione moieties are shown in black and the spermidine linker in red.

Professor Alan Fairlamb, and his team study the protozoan parasites causing three different diseases - sleeping sickness, Chagas disease and leishmaniasis. He was one of the 250 scientists involved in the genome sequencing of these parasites.[1]

In 1985, Alan Fairlamb discovered a unique thiol compound present in these parasites, and named it trypanothione.[2] This thiol metabolite is quite different from its human equivalent, glutathione. Trypanothione allows the parasites to fend off free radicals and other toxic oxidants produced by the immune system of the infected patient, and was shown to be vital for parasite survival and virulence.[3] For instance, antimonials neutralize the Leishmania parasite's antioxidant defence system, allowing the patient to clear the infection.[4] Studies on the effect of drugs on trypanothione metabolism resulted in the discovery that fexinidazole is a potential oral treatment for visceral leishmaniasis.[5]

Since 2006, Alan Fairlamb and Mike Ferguson have been co-directors of the Drug Discovery Unit at the University of Dundee. The new centre, opened in 2005, has facilities for high-throughput screening and medicinal chemistry.[6] These will take the drug discovery/development process further than any other UK university, to a stage where pharmaceutical companies will have sufficient data to move into the production stage.

References

  1. Berriman M, Ghedin E, Hertz-Fowler C, et al. (2005). "The genome of the African trypanosome Trypanosoma brucei". Science. 309 (5733): 416–22. Bibcode:2005Sci...309..416B. doi:10.1126/science.1112642. PMID 16020726.
  2. Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A (1985). "Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids". Science. 227 (4693): 1485–7. Bibcode:1985Sci...227.1485F. doi:10.1126/science.3883489. PMID 3883489.
  3. Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, Clayton C (2000). "Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress". Mol. Microbiol. 35 (3): 542–52. doi:10.1046/j.1365-2958.2000.01721.x. PMID 10672177.
  4. Wyllie S, Cunningham ML, Fairlamb AH (2004). "Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani". J. Biol. Chem. 279 (38): 39925–32. doi:10.1074/jbc.M405635200. PMID 15252045.
  5. Wyllie,S.; Patterson,S.; Stojanovski,L.; Simeons,F.R.; Norval,S.; Kime,R.; Read,K.D. & Fairlamb AH (2012). "The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis". Sci. Transl. Med. 4: 119re1. doi:10.1126/scitranslmed.3003326. PMC 3457684. PMID 22301556.
  6. University hunts cure for parasitic infections Tim Radford, The Guardian, Wednesday 26 October 2005
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