Expression of multi-gene families in Plasmodium falciparum

Dr. A. Rowe

Severe malaria is caused by the adhesion of red blood cells infected with P. falciparum to host cells (endothelium and uninfected red blood cells to form rosettes). Work is currently underway to understand the receptor-ligand interactions that bring about this adhesion. Members of two multi-gene families, var genes and rif genes have so far been implicated as parasite ligands mediating adhesion. The P. falciparum genome project has recently identified four more multi-gene families of unknown function. The aim of this project is to characterise these novel multi-gene families in terms of stage-specific expression and cellular localisation, and to determine if they also play a role in parasite adhesion and therefore are important in the pathogenesis of malaria.

References

Bowman S et al (1999). The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 400: 532-538.

Rowe J A, Kyes S A, Kriek N & Newbold C I (1999). Rifins: A second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proceedings of the National Academy of Sciences of the USA 96: 9333-9338.

Rowe J A, Moulds J M, Newbold C I & Miller L H (1997). P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388: 292-295.

 

Complement receptor 1 polymorphisms and susceptibility to severe malaria

Complement receptor 1 (CR1) is a receptor for the adhesion of Plasmodium falciparum-infected red blood cells to uninfected red blood cells to form rosettes. The ability to rosette is a parasite adhesion property that is associated with severe malaria and may play a direct role in the pathology of severe disease. A CR1 polymorphism that leads to a deficiency of CR1 on red cells occurs rarely in most populations, but is thought to be common in Melanesians living in malaria endemic areas. The aim of this project is to study the incidence of this and other CR1 polymorphisms in Melanesians, and determine if they influence susceptibility to malaria. This project will involve collaboration with workers in Vanuatu, Papua New Guinea and the US.

Rowe JA, Moulds JM, Newbold CI & Miller LH (1997). P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388: 292-295.

Molthan, L. (1983) The status of the McCoy/Knops antigens. Medical Laboratory Sciences 40, 59-63.

Moulds, J. M., Nickells, M. W., Moulds, J. J., Brown, M. C. & Atkinson, J. P. (1991) The C3b/C4b receptor is recognized by the Knops, McCoy, Swain-Langley and York blood group antisera. Journal of Experimental Medicine 173, 1159-1163.

Daniels, G. (1995) Knops blood group system and Cost antigens, in Human Blood Groups (Blackwells Scientific, Oxford), pp. 582-593.