Laboratory of Dr David Conway
Project 1
Mapping protective epitopes on polymorphic Plasmodium falciparum antigens by molecular population genetic and immunological analyses
Objectives:
To identify targets of protective immunity which could form the basis of a vaccine, with the following procedures
- Identify sequence sites under natural selection in P. falciparum antigens (particularly merozoite proteins MSP1 - 3, AMA1, EBA-175) by molecular population genetic analyses
- Construct recombinant polypeptides representing these antigenic regions
- Test if naturally-acquired antibodies recognising these are associated with protection from malaria
- Map antibody epitopes more finely in promising antigenic regions, test for presence of human T cell epitopes, and construct optimal immunogens for vaccination studies
Participants in the project:
- David.Conway@lshtm.ac.uk
- Spencer Polley
- Kevin Tetteh
- Jennie Lloyd
Output from the project:
- Conway, D.J., Cavanagh, D.R., Tanabe, K., Roper, C., Mikes, Z.S., Sakihama, N., Bojang, K.A., Oduola, A.M.J., Arnot, D.E., Greenwood, B.M., and McBride, J.S. (2000). A principal target of human immunity to malaria identified by molecular population genetic and immunological analysis. Nature Med. 6: 689-692
- Okenu, D.M.N., Thomas, A.W., and Conway, D.J. (2000). Allelic lineages of the merozoite surface protein 3 gene in Plasmodium reichenowi and Plasmodium falciparum. Mol. Biochem. Parasitol. 109: 185-188.
- Kocken, C.H.M., Narum, D.L., Massougbodji, A., Ayivi, B., Dubbeld, M.A., van der Wel, A., Conway, D.J., Sanni, A., and Thomas, A.W. (2000). Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1 (AMA-1), comparison with P. falciparum AMA-1, and antibody-mediated inhibition of red cell invasion. Mol. Biochem. Parasitol. 109: 147-156
- Okenu, D.M.N., Riley, E.M., Bickle, Q.D., Agomo, P.U., Barbosa, A., Daugherty, J.R., Lanar, D.E., and Conway, D.J. (2000). Analysis of human antibody responses to erythrocyte binding antigen-175 of Plasmodium falciparum. Infect. Immun. 58: 5530-5538.
- Binks, R.H., Baum, J., Oduola, A. M. J., Kremsner, P.G., Arnot, D.E., Babiker, H., Roper, C., Greenwood, B.M., and Conway, D.J. Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (eba-175) gene. Mol. Biochem. Parasitol., in press.
- Binks, R.H., and Conway, D.J. (1999). The major allelic dimorphisms in four Plasmodium falciparum merozoite proteins are not associated with alternative pathways of erythrocyte invasion. Mol. Biochem. Parasitol. 103: 123-127.
- Conway, D.J. (1997). Natural selection on polymorphic malaria antigens and the search for a vaccine. Parasitol. Today, 13: 26-29
Project 2
Empirically determining important aspects of the population genetics of Plasmodium falciparum
Objectives:
To determine the molecular population genetic parameters which have a genome-wide impact on Plasmodium falciparum. These characterise the basic genetic structure of the species, and affect the design and interpretation of studies to identify functionally important genes. They include
- Effective recombination rate
- Population substructure and geographical restrictions to gene flow
- Genetic history of populations globally
- Genetically effective population size
Participants in the project:
- David.Conway@lshtm.ac.uk
- Cally Roper
- Watcharee Chokejindachai
Output from the project:
- Conway, D.J., Fanello, C.Lloyd, J., Al-Joubori, B.M.A-S, Baloch, A.H., Somanath, S.D., Roper, C., Oduola, A.M.J., Mulder, B., Povoa, M., Singh, B., and Thomas, A.W. (2000). Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol. Biochem. Parasitol. 111: 137-145
- Conway, D.J., Roper, C., Oduola, A.M.J., Arnot, D.E., Kremsner, P.G., Grobusch, M.P., Curtis, C.F., and Greenwood, B.M. (1999). High recombination rate in natural populations of Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 96: 4506-4511
- Sakihama, N., Kimura, M., Hirayama, K., Kanda, T., Na-Bangchang, K., Jongwutiwes, S., Conway, D., and Tanabe, K. (1999). Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite. Gene 230: 47-54
- Conway, D.J. and Roper, C. (2000). Micro-evolution and emergence of pathogens. Int. J. Parasitol. 30: 1423-1430
