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Margaret Mackinnon
kilifi [dot] kemri-wellcome [dot] org Research
What is it that causes pathogens to harm their host? In my lab, we study the evolutionary pressures, and the biology underlying them, that make pathogens virulent. We focus particularly on human malaria parasites since these cause enormous amounts of disease throughout the developing world. We are trying to find out which parasite genes are responsible for causing severe disease, and what factors control their gene expression levels.
We also study the consequences of pathogen evolution to disease burden at the population level. Our main question is whether by using control programmes that reduce or enhance levels of immunity (e.g. by using bednets or vaccines), we will select for parasites that have lower or higher virulence. If so, the question then becomes "How would these evolutionary changes in the parasite population enhance or offset the positive benefits of the control programme?" We use a combination of microarray-based investigations of parasite populations (using our newly acquired microarray facility) and evolutionary-epidemiological mathematical models of malaria to study questions such as these.
In collaboration with other groups in Cambridge, Oxford, Melbourne and Edinburgh, we maintain a working interest in the host genetic basis of resistance to malaria, parasite population genetics and antigenic cartography.
Collaborations
Publications
Mackinnon M.J., Li, J., Mok, S., Kortok, M.M., Marsh, K., Preiser, P.R., Bozdech, Z. (2009) Comparative transcriptional and genomic analysis of Plasmodium falciparum field isolates. PLoS Pathogens 5: (10).
Bejon P, Warimwe G, Mackintosh CL, Mackinnon M.J., Kinyanjui SM, Musyoki JN, Bull PC, Marsh K (2009) Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun 77: 1917-1923.
Mwai L, Ochong E, Abdirahman A, Kiara SM, Ward S, Kokwaro G, Sasi P, Marsh K, Borrmann S, Mackinnon M.J., Nzila A (2009) Chloroquine resistance before and after its withdrawal in Kenya. Malar J 8: 106.
Mackinnon, M. J., Gandon, S., Read, A. F. Virulence evolution in response to vaccination: the case of malaria (2008). Vaccine 26S:C42-52.
Osier, F.H.A., Fegan, G., Polley, S.D., Murungi, L., Verra, F., Tetteh, L.K..A., Lowe, B., Mwangi, T., Bull, P.C., Thomas, A.W., Cavanagh, D.R., McBride, J.S., Lanar, D.E., Mackinnon, M.J., Conway, D.J., Marsh, K. (2008) Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect. Immun. 76:2240-2248.
Dobano, C., Rogerson, S.J., Mackinnon, M.J., Cavanagh, D.R., Taylor, T.E., Molyneux, M.E., McBride, J.S. (2008) Differential antibody responses to Plasmodium falciparum merozoite proteins in Malawian children with severe malaria J. Inf. Diseases 197(5):766-74.
Read, A.F. and Mackinnon, M.J. (2008) Pathogen evolution in a vaccinated world. Chapter 11, pp139-152. Book chapter in ‘Evolution in Health and Disease’, Stearns, S.C. and Koella, J. C. (Eds). Oxford University Press
Deans, A., Lyke, K. E., Thjera, M.A., Plowe, C. V., Kone, A., Doumbo, O. K., Kai, O., Marsh, K., Mackinnon, M. J., Raza, A., Rowe, J.A. (2006). Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red cell selectivity with malaria virulence. Am. J. Trop. Med. Hyg. 74(4):554-563.
Ali,E., Mackinnon,M.J., Abdel-Muhsin,A.M., Ahmed,S., Walliker,D. and Babiker,H.A. Increased gametocytaemia following drug treatment of Plasmodium falciparum in Sudan (2006) Trans. R. Soc. Trop. Med. Hyg. 100(2):176-183.
Ferguson,H.F., Gandon,S., Mackinnon, M.J. and Read, A.F. (2006) Malaria parasite virulence in mosquitoes and its implications for the introduction and efficacy of GMM malaria control programmes. In ‘Genetically modified mosquitoes for malaria control’ Ed. Boete, C. Landes Bioscience.
Mackinnon, M.J., Mwangi, T., Snow, R., Marsh,K. & Williams, T.N. (2005) Heritability of malaria in Africa. PloS Medicine 2 (12) e340.
Mackinnon, M.J. (2005) Drug resistance models in malaria. Acta Trop. 94: 207-217
Martinelli, A., Cheesman, S.J., Hunt, P., Culleton, R., Raza, A., Mackinnon, M.J. and Carter, R. (2005). A genetic approach to the de novo identification of targets of strain-specific immunity in malaria parasites. Proc. Natl. Acad. Sci. USA 102: 814-819.
Mackinnon, M.J. and Read, A.F. (2004) Immunity promotes virulence evolution in a malaria model. PloS Biology. 2 (9) e230, pp1286-1292.
Cockburn, I.A., Mackinnon, M.J., O'Donnell, A., Allen, S.J., Moulds, J.M., Baisor, M., Bockarie, M., Reeder, J.C. and Rowe, J.A. (2004) A human complement receptor one polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc. Natl. Acad. Sci. USA 101:272-277.
Mackinnon, M.J. and Read, A.F. (2003) The effects of host immunity on virulence-transmissibility relationships in the rodent malaria parasite Plasmodium chabaudi. Parasitology. 126:103-112.
*Gandon, S., *Mackinnon, M.J., Nee, S. and Read, A. F. (2001) Imperfect vaccines and the evolution of pathogen virulence. Nature 414:751-756. * denotes joint first authorship
Mackinnon, M.J., Gunawardena, D. M., Rajakaruna, J., Weerasingha, S. W., Mendis, K. N., and Carter, R. (2000) Quantifying genetic and non-genetic contributions to malarial infection in a Sri Lankan population. Proc. Natl. Acad. Sci. USA 97:12661-12666.
Mackinnon, M.J. and Read, A.F. (1999). Genetic relationships between parasite virulence and transmission in the rodent malaria Plasmodium chabaudi. Evolution 53: 689-703.
Mackinnon, M.J. and Read, A.F. (1999). Selection for high and low virulence in the malaria parasite Plasmodium chabaudi. Proc. Roy. Soc. Lond. B. 266: 741-748.