Signalling in malaria parasites – The MALSIG consortium

Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i) the properties of Plasmodium signalling molecules, and ii) developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei) are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years. Les parasites responsables du paludisme sont confrontés à des environnements extrêmement divers au cours du cycle parasitaire ; ils peuvent se trouver dans la circulation sanguine chez l’hôte vertébré et hémocoele chez le moustique vecteur, ainsi qu’à l’intérieur de divers types cellulaires (hépatocytes et érythrocytes de l’hôte vertébré, intestin et glandes salivaires de l’insecte). Les mécanismes moléculaires et cellulaires permettant au parasite de reconnaître et de répondre à ces environnements intra ou extracellulaires jouent un rôle crucial dans sa survie et son programme développemental, tant pour la prolifération que pour la transmission au vecteur, et représentent donc des cibles potentielles pour l’interven