Biomedical and Life Sciences

Dr Paul McKean

Senior Lecturer

Office C18, Lab C5/9
Division of Biomedical and Life Sciences
Faculty of Health and Medicine
Lancaster University
Lancaster
LA1 4YQ
UK

Tel: +44 1524 594717
Fax: (44) 1524 593192
Email: p.mckean@lancaster.ac.uk

Research Interests

The major research interest of my laboratory is in the cell biology of the flagellated protozoan parasites Trypanosoma brucei and Leishmania major. My interest in these organisms is two-fold: firstly because these organisms are parasites of medical and veterinary importance; and secondly because they are useful model organisms in which to study the biogenesis of the eukaryotic flagellum. As in most eukaryotic cells, the flagellum of these protozoan cells possess a typical 9+2 microtubule axonemal structure consisting of 9 outer doublet microtubules and a pair of central singlet microtubules.

As part of a BBSRC funded initiative my lab is collaborating with Prof. Keith Gull (Sir William Dunn School of Pathology, University of Oxford) and Prof. Simon Gaskell (UMIST, Manchester) to compile a complete proteomic catelogue of proteins required to build the eukaryotic flagellum. By providing a better understanding of the molecular composition of the eukaryotic flagellum/cilium we aim to provide a greater awareness of diseases such as primary ciliary dyskinesia (PCD) that are characterised by functional and/or structural abnormalities of cilia (and sperm). In this project we are collaborating with Dr Hannah Mitchison and her colleagues at UCL, London who are currently mapping loci involved in the development of PCD.

Education

BSc (Hons) Zoology, University of Nottingham, 1985
Ph.D. University of Nottingham, 1989

Academic positions

1989 -1992 Postdoctoral research assistant, Division of Parasitology, National Institute for Medical Research, Mill Hill London
Beit Memorial Fellow for Medical Research, Department of Biochemistry, Imperial College, London.
1995 -1999 Postdoctoral research assistant, Department of Biochemistry, Imperial College, London.
1999 - 2001 Research Fellow, School of Biological Sciences, University of Manchester
Lecturer in Biological Sciences, Lancaster University
Senior Lecturer in Biological Sciences, Lancaster University

Publications

Ginger, M.L., Portman, N. and McKean, P.G. (2008)Swimming with protists: perception, motility and flagellum assembly. Nature Reviews in Microbiology 6(11):838-850

Hart, S.R., Lau, K.W., Hao, Z., Broadhead, R., Portman, N., Huhmer, A., Gull, K., McKean, P.G., Hubbard, S.J. and Gaskell, S.J. (2008) Analysis of the Trypanosome Flagellar Proteome Using a Combined Electron Transfer/Collisionally Activated Dissociation Strategy. Journal of the American Society for Mass Spectrometry – In Press

Stephan, A., Vaughan, S., Shaw, M.K, Gull K. and McKean, P.G. (2007) An essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport. Traffic 8(10):1323-30

Hammarton, T., Wickstead, B. and McKean P.G. (2007) Cell structure, cell division and cell cycle. In: Trypanosomes -After the Genome. Eds. Barry, D., McCulloch, R., Mottram, J. and Acosta-Serrano, A. Published by Horizon Bioscience.

Davidge, J.A., Chambers, E, Dickinson, H.A., Towers, K, Ginger, M.L., McKean, P.G. and Gull, K. (2006) Trypanosome IFT mutants provide insight into the motor location for mobility of the flagella connector and flagellar membrane formation. Journal of Cell Science 119(19):3935-3943

Gadelha, C., Wickstead, B. Mckean, P.G. and Gull, K.(2006) Basal body and flagellum mutants reveal a rotational constraint of the central pair microtubules in the axonemes of trypanosomes. Journal of Cell Science 119(12):2305-2413

Broadhead, R., Dawe, H.R., Farr, H., Griffiths, S., Hart, S.R., Portman, N., Shaw, M.K., Gaskell, S.J., McKean, P.G. and Gull, K. (2006) Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 440:224-227

Briggs, L., McKean, P.G., Baines, A., Moreira-Leite, F., Davidge, J., Vaughan, S. and Gull, K. (2004) The flagella connector of Trypanosoma brucei: an unusual mobile transmembrane junction. Journal of Cell Science 117(9):1641-1651

McKean, P.G. (2003) Coordination of cell cycle progression and cytokinesis in Trypanosoma brucei. Current Opinion in Microbiology 6(6):600-607

McKean, P.G., Baines, A., Vaughan, S. and Gull, K. (2003) γ-tubulin functions in the nucleation of a discrete sub-set of microtubules in the eukaryotic flagellum. Current Biology 13(7):598-602

Price, H.P., Menon, M.R, Panethymitaki, C., Goulding, D., McKean,P.G. and Smith, D. F. (2003) Myristoyl CoA: protein N-myristoyltransferase, an essential enzyme and potential drug target in kinetoplastid parasites. Journal of Biological Chemistry 278: 7206 - 7214

O'Dea, K.P., McKean, P.G. and Brown, K.N. (2002) Plasmodium chabaudi chabaudi AS: modification of acute infection in CBA/Ca mice as a result of pre-treatment with erythrocyte band 3 in adjuvant. Experimental Parasitology 102:66-71

McKean, P.G., Vaughan, S. and Gull, K. (2001) The extended tubulin superfamily. Journal of Cell Science 114(15): 2723-2733

McKean, P.G. Denny, P. W., Kneupfer, E., Keen, J.K. and Smith, D. F. (2001) Phenotypic changes associated with deletion and over-expression of a stage-regulated gene family in Leishmania. Cellular Microbiology 3(8): 511-523

McKean, P.G., Keen, J.K. Smith, D. F. and Benson, F.E. (2001) Identification and characterisation of a RAD51 gene from Leishmania major. Molecular and Biochemical Parasitology 115(2):209-216

Kneupfer, E., Stierhof, Y. D., McKean, P.G. and Smith, D. F. (2001) Characterisation of a differentially expressed protein that shows an unusual localisation to intracellular membranes in Leishmania major. The Biochemical Journal 356(2):335-344

Vaughan, S., Attwood, T., Navarro, M., Scott, V., McKean, P and Gull, K. (2000) New tubulins in protozoal parasites. Curr Biol. 10(7):R258-9

McKean, P.G., Keen, J.K., Kelly, J.M. and Smith, D.F. (1999) Molecular parasitology: new insights.Parasitol Today. 15(12):469-70

McKean, P.G., Trenholme, K.R., Rangarajan, D., Keen, J.K. and Smith, D.F. (1997) Diversity in repeat-containing surface proteins of Leishmania major. Mol Biochem Parasitol. 86(2):225-35

Mckean, P.G., Delahay, R., Pimenta, P.F. and Smith, D.F. (1997) Characterisation of a second protein encoded by the differentially regulated LmcDNA16 gene family of Leishmania major. Mol Biochem Parasitol. 85(2):221-31

O’Dea, K.P., McKean, P.G., Jarra, W. and Brown, K.N. (1996) A single gene copy merozoite surface antigen and immune evasion? Parasite Immunol. 18(4):165-72

O’Dea, K.P., McKean, P.G., Harris, A. and Brown, K.N. (1995) Processing of the Plasmodium chabaudi chabaudi AS merozite surface protein 1 in vivo and in vitro. Mol Biochem Parasitol 72(1-2):111-9

Smith, D.F., Gokool, S., Keen, J.K., McKean, P.G. and Rangarajan, D. (1994) Structure and function of infective stage proteins of Leishmania. Biochem Soc Trans. 22(2):286-91. Review

McKean, P.G., O’Dea, K.P. and Brown, K.N. (1993) A single amino acid determines the specificity of a monoclonal antibody which inhibits Plasmodium chabaudi ASin vivo. Mol Biochem Parasitol. 62(2):211-21

McKean, P.G., O’Dea, K.P. and Brown, K.N. (1993) Nucleotide sequence analysis and epitope mapping of the merozoite surface protein 1 from Plasmodium chabaudichabaudi AS. Mol Biochem Parasitol. 62(2):199-209

Pritchard, D.I., Quinnell, R.J., McKean, P.G., Walsh, L., Leggett, K.V., Slater, A.F., Raiko, A., Dale, D.D., Keymer, A.E. (1991) Antigenic cross-reactivity between Necator americanus and Ascaris lumbricoides in a community in Papua New Guinea infected predominantly with hookworm. Trans R Soc Trop Med Hyg. 85(4):511-4

Pritchard, D.I., Leggett, K.V., Rogan, M.T., McKean, P.G. and Brown, A. (1991) Necator americanus secretory acetylcholinesterase and its purification from excretory-secretory products by affinity chromatography. Parasite Immunol. 13(2):187-99

Pritchard, D.I., Quinnell, R.J., Moustafa, M., McKean, P.G., Slater, A.F., Raiko, A., Dale, D.D., Keymer, A.E. (1991) Hookworm (Necator americanus) infection and storage iron depletion. Trans R Soc Trop Med Hyg. 85(2):235-8

Pritchard, D.I., Quinnell, R.J., Slater, A.F., McKean, P.G., Dale, D.D., Raiko, A., Keymer, A.E. (1990) The epidemiological significance of the immune response to thecuticular collagen of Necator americanus: a preliminary study in a hookworm-endemic areain Papua New Guinea. Acta Trop. 47(5-6):403-7

Pritchard, D.I., McKean, P.G., Rogan, M.T. and Schad, G.A. (1990) The identification of a species-specific antigen from Necator americanus. Parasite Immunol. 12(3):259-67

Pritchard, D.I., Quinnell, R.J., Slater, A.F., McKean, P.G., Dale, D.D., Raiko, A., Keymer, A.E. (1990) Epidemiology and immunology of Necator americanus infection in acommunity in Papua New Guinea: humoral responses to excretory-secretory and cuticular collagen antigens. Parasitology. 100 Pt 2:317-26

McKean, P.G. and Pritchard, D.I. (1989) The action of a mast cell protease on the cuticular collagens of Necator americanus. Parasite Immunol. 11(3):293-7