Variation in commitment to sexual development in the malaria parasite Plasmodium falciparum

Prof David Conway (primary)
Department of Infection Biology
London School of Hygiene and Tropical Medicine
Prof David Baker (secondary)
Department of Infection Biology
London School of Hygiene and Tropical Medicine

Abstract

Malaria parasites in the blood need to switch from asexual to sexual forms to be able to infect mosquitoes and be transmitted to other hosts. Plasmodium falciparum parasites in humans vary widely in rates of commitment to switch, and this is associated with parasite variation at a key controlling gene (gdv1) with major alleles being differentially selected among local populations in Africa. This project will use powerful new bioinformatic and experimental approaches to resolve whether the causal determinants are within the coding sequence or regulatory intergenic sequences, and to unravel the molecular mechanisms of regulation and initial development to sexuality.


References

Duffy, C.W., Amambua-Ngwa, A., Ahouidi, A.D., Diakite, M., Awandare, G.A., Ba, H, Tarr, S.J., Murray, L., Stewart, L.B., D’Alessandro, U., Otto, T.D, Kwiatkowski, D.P., & Conway, D.J. (2018) Multi-population genomic analysis of malaria parasites indicates local selection and differentiation at the gdv1 locus regulating sexual development. Scientific Reports, 8:15763. doi: 10.1038/s41598-018-34078-3.

Tarr, S.J., Diaz-Ingelmo, O., Stewart, L.B., Hocking, S., Murray, L., Duffy, C.W., Otto, T.D., Chappell, L., Rayner, J.C. Awandare, G.A. & Conway, D.J. (2018) Schizont transcriptome variation among clinical isolates and laboratory-adapted clones of the malaria parasite Plasmodium falciparum. BMC Genomics, 19:894. doi: 10.1186/s12864-018-5257-x.

Murray, L., Stewart, L.B., Tarr, S.J., Ahouidi, A.D., Diakite, M., Amambua-Ngwa, A., & Conway, D.J. (2017) Multiplication rate variation in the human malaria parasite Plasmodium falciparum. Scientific Reports, 7:6436. doi: 10.1038/s41598-017-06295-9.

Claessens, A., Affara, M., Assefa, S.A., Kwiatkowski, D.P. & Conway, D.J. (2017) Culture adaptation of malaria parasites selects for convergent loss-of-function mutants. Scientific Reports, 7:41303, doi: 10.1038/srep41303.

Mobegi, V.A., Duffy, C.W., Amambua-Ngwa, A., Loua, K.M., Laman, E., Nwakanma, D.C., MacInnis, B., Aspeling-Jones, H., Murray, L., Clark, T.G., Kwiatkowski, D.P., & Conway, D.J. (2014) Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in West African populations of differing infection endemicity. Molecular Biology and Evolution, 31:1490-1499, doi: 10.1093/molbev/msu106.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
GeneticsMicrobiology
Techniques & Approaches
BioinformaticsGeneticsMolecular Biology