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MalariaPorin


Malaria

Validation of the Plasmodium Aquaglyceroporin as a Drug Target
Framework programme:
6
Call:
2
Project number:
LSHP- CT-2004-012189
EC contribution:
€ 885,534
Duration:
27 months
Type:
STREP
Starting date:
1 January 2005

Keywords: Malaria; aquaglyceroporin; assay systems; drug development

Summary:

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.

Background:

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.

Aim:

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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