Use of peptides from phage display libraries to probe the function of AMA-1 and other malaria surface proteins

Funded Activity Summary

Malaria remains a major cause of mortality and morbidity worldwide. Much current research is aimed at exploring the molecular interactions between malarial proteins and host components in order to gain a deeper understanding of parasite virulence mechanisms, design alternative anti-malarial approaches and improve vaccine design. The apical membrane antigen-1( AMA-1) is a surface exposed protein which is thought to play a crucial role in invasion of red blood cells by malaria parasites, and is currently one of the leading asexual stage vaccine candidates. While antibodies to AMA-1 prevents malaria invasion, little is known about the role of the antigen in the invasion process. The aim of this proposal is to investigate the molecular interactions that makes AMA-1 an important player in the invasion process. We propose to map the regions of AMA-1 responsible for binding a set of peptides which we have isolated from random peptide libraries. Since these peptides inhibit the invasion of parasites into red blood cells, regions of AMA1- that bind these peptides will be of functional significance. A further outcome will be the identification of peptide residues essential for the inhibition of invasion followed by in vitro evolution of these peptides to improve their binding and inhibitory properties. A molecular description of how AMA1 binding peptides prevent parasite invasion of host erythrocytes will improve our understanding of the invasion process, and aid in improving vaccines based on AMA-1. Furthermore, this peptide-AMA-1 interaction will be assessed as a possible target for the development of novel anti-malarial therapies. Using random peptide libraries we have selected peptides that specifically bind to other merozoite surface proteins thought to be involved in merozoite invasion of erythrocytes. The ability of these peptides to inhibit merozoite invasion will be examined and characterised as described above.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $316,650.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Humoural immunology and immunochemistry

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Plasmodium falciparum | malaria | merozoite invasion | parasite | phage display | random peptides | therapy

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