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Validation of the Plasmodium Aquaglyceroporin as a Drug Target
Framework programme:
Project number:
LSHP- CT-2004-012189
EC contribution:
€ 885,534
27 months
Starting date:
1 January 2005

Keywords: Malaria; aquaglyceroporin; assay systems; drug development


MalariaPorin is an interdisciplinary project that wants to evaluate the suitability of the single aquaglyceroporin of the parasite-host-interface as a novel drug target.


Malaria is one of the three major infectious diseases. Although the disease is prevalent in the tropics and sub-tropics, it has caused a global emergency. Three to four hundred million cases, with 1-2 million deaths per year and rapidly increasing resistance to antimalarial drugs call for focused novel strategies on combating malaria. Transport proteins for nutrients and metabolites of the minimal parasite/host interface are getting into the focus of the current search for novel antimalarial targets.


The chief goal is to decide on the question whether the Plasmodium water and glycerol channel, aquaglyceroporin, of the parasite/host interface is a suitable drug target for chemotherapy. At the same time, the conditions for generating aquaglyceroporin inhibitory drugs are to be developed.

Expected results:

To achieve these goals, a multidisciplinary approach will be taken. This will cover a) thorough studies on the physiological role of water and glycerol transport in the malaria parasite, including the generation of deletion strains; b) establishment of robust and practical assay systems for compound testing based on Xenopus laevis oocytes, yeast and P. falciparum parasites; c) determination from field isolates of the occurrence and functional consequences of polymorphisms of the aquaglyceroporin gene; d) generation of protein structure models and elucidation of the 3D structure from protein crystallisation for solving mechanistic questions on the channel selectivity and for virtual drug design; e) design and synthesis of compound libraries based on the knowledge of other aquaporin blockers and biochemical studies of substrate specificity.

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