Framework programme:

 7

Contract/Grant agreement number:

223044

EC contribution:

3.000.000 €

Funding scheme:

Collaborative project (SICA)

Starting date:

01/02/2009

 

 

Keywords: malaria, Plasmodium, signalling, phosphorylation, invasion, sexual development, exoerythrocytic schizogony, trafficking.

Background

Our knowledge and understanding of the basic biology of malaria parasites is still fragmentary. This is particularly true with respect to the molecular mechanisms that regulate progression through the different stages of the parasite’s life cycle in the human host and the mosquito vector.

The development of novel strategies for malaria control requires a better understanding of the biology of malaria parasites. MALSIG aims at bringing a significant contribution to this field by dissecting the signalling pathways that regulate essential processes in the life cycle of malaria parasites. The proposed research will merge two lines of investigation that have thus far been conducted largely independently from each other, namely:

• the characterisation of components of signal transduction pathways (protein kinases, nucleotide cyclases, calcium signalling mediators) in malaria parasites;
• the study of specific biological and developmental processes during the life cycle of malaria parasites.

Merging these two fields of malaria research will ensure a high level of complementarity and synergy within the consortium. Specific work packages (WPs) will be centred on understanding signalling-dependent regulation in the following processes and stage transition within the life cycle of malaria parasites:

• erythrocyte infection (invasion, parasite proliferation, egress);
• sexual development (gametocytogenesis, gametogenesis, transmission to the mosquito vector);
• hepatocyte infection (invasion, parasite proliferation, egress);
• membrane dynamics (trafficking, transporters).

Approaches will include proteomics, reverse genetics, structural biology, and the use of animal models of malaria.

The consortium includes both EU and Indian partners with proven track records either in research into one of the developmental stages/processes described above, or in signal transduction in malaria parasites. The project will significantly strengthen EU-Indian cooperation in this highly relevant topic.

Aims and expected results

The general aim of the project is to advance current knowledge of the organisation of signalling pathways in malaria parasites and of their roles in the transition between developmental stages of the Plasmodium life cycle.

Merging investigations on signalling pathways on one hand, and on specific aspects of Plasmodium cell biology on the other, is expected to have a high impact on our knowledge of the basic biology of malaria parasites. In particular, it is expected that new insights will be gained with respect to the signalling events regulating crucial processes in the life cycle, such as invasion of host cells, sexual development, transmission to the mosquito vector, cellular trafficking and small molecule transport across membranes.

Furthermore, cooperation within the consortium will result in the strengthening of national and transnational malaria research.

Potential applications:

The MALSIG research programme addresses the fundamental biology of malaria parasites, a prerequisite for the rational development of subsequent translational research. The long-term goal in furthering the understanding of signalling events is to discover novel targets for antimalarial drug and vaccine development. Several MALSIG partners are indeed engaged separately in drug/vaccine discovery programmes.

Coordinator:

Christian Doerig
Inserm U609, University of Glasgow
Glasgow
UK
christian.doerig@epfl.ch

Project Manager:

Virginie Chameroy
Inserm ADR Lille
Lille
France
virginie.chameroy@inserm.fr

Partners:

Affiliated Members: