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Plasmodium falciparum Malaria: Exploring sub-telomeric genes with the novel proteomics method "SURFEOMICS"

Plasmodium falciparum Malaria: Exploring sub-telomeric genes with the novel proteomics method "SURFEOMICS"

Objective

Malaria kills a child every 40 seconds. Up to 500 million malaria cases are estimated each year, resulting in more than a million deaths. The malaria parasite Plasmodium falciparum is one of the greatest health problems in the developing world. This project will test the hypothesis that the blood stage of the malaria parasite (merozoite) depends on multiple expressed ligands (rather than only one) for both adhering to and invading erythrocytes. Novel variable polypeptides termed SURFINs, which are encoded b y the surf-gene family, were recently discovered on both the infected erythrocyte (IE) and merozoite surface. In addition, other new gene families have been identified in the sub-telomeric regions of the P. falciparum chromosomes.

The identification of the se polypeptides suggests that antigenic variation also occurs at the merozoite level and that the parasite coordinates antigen expression. Furthermore, it argues that multiple molecules have important roles in both IE adhesion and merozoite invasion into t he erythrocyte. Studies will focus on identifying new ligands using a proteomic approach termed 'surfeomics', which targets protein moieties displayed on the surface of live IEs. Parasite surface proteins are removed using a trypsin digest and identified by mass spectrometry. Results will be used to create a database containing parasite surface proteins linked to genomic data.

This database will augment the existing PlasmaDB database and provide information on surface protein variation and its relationship to parasite strain, life stage, and virulence. This research will increase our understanding of malaria pathogenesis by combining in silico bioinformatics and in vitro molecular experiments. Expressed surface proteins are important in the ability of theme rozoite to evade the human immune system, and are a target for malaria vaccine development. These research findings could be an important step in alleviating malaria-induced suffering in the developing world.

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Coordinator

KAROLINSKA INSTITUTET

Address

Nobels VÄG 5
Stockholm

Sweden

Administrative Contact

Mats WAHLGREN (Prof.)

Project information

Grant agreement ID: 21534

  • Start date

    20 April 2006

  • End date

    19 April 2008

Funded under:

FP6-MOBILITY

Coordinated by:

KAROLINSKA INSTITUTET

Sweden