Europe joins India in the fight against malaria European and Indian researchers teamed up to study the signalling pathways necessary for the survival and transmission of the malaria-causing parasite (Plasmodium falciparum). Some of the molecules detected could potentially serve as future targets for therapeutic intervention. Health © Thinkstock Malaria remains a major health issue in the developing world with over 70 million clinical cases annually reported in India alone. In view of the emerging resistance of the malaria parasite to existing control measures, novel strategies are urgently required. This necessitates an in-depth understanding of the biology and life cycle of the parasite. The EU-funded MALSIG project was initiated to characterise the molecular components of signalling pathways implicated in the life cycle of malaria parasites. To this end, the consortium focused on three stages of the parasite life cycle — erythrocyte (red blood cell) invasion, sexual development and hepatocytes’ (liver) infection. Detailed information can be found on the project website. Project results elucidate the importance of various second messengers (calcium, cAMP and phospholipase C) and protein kinases (CDPK5 and PKG) in the erythrocyte invasion stage. The subcellular location and assembly of the parasite motor complex was also delineated, providing detailed information on its development. Besides identifying a host erythrocyte signalling pathway and several protein kinases critical for parasite survival, a scalable transfection tool was developed for testing drug efficacy. Using reverse genetics and knockout lines, the consortium proceeded to elucidate the signalling components, effector molecules and stage-specific processes implicated in the parasite's sexual development. Calcium-dependent protein kinase 1 (CDPK1) in P.falciparum was found to be indispensable during the sexual stages of its life cycle. The effector Alveolin IMC1h was essential for normal motility behaviour and accessing the bloodstream. MALSIG research revealed that infected erythrocytes are more deformable than immature ones, possibly playing an important role in P. falciparum gametocyte development in the host. Various transgenic parasite strains were generated by researchers for molecular analysis of the parasite–host cell interaction during the liver-infecting phase of the parasite.This enabled scientists to elucidate the function of parasite proteins and their localisation in different stages of liver invasion and infection. A novel role for the messenger phosphatidylinositol-3-kinase (PI3K) was identified in the digestion of haemoglobin and acquisition of essential amino acids by P. falciparum. Taken together, MALSIG project findings provided a series of signalling, trafficking, motility and transporter molecules that are essential for specific stages of the life cycle of the malaria parasite. These molecules represent novel and unconventional targets for interfering with parasite transmission.
