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MalariaPorin


Validation of the plasmodium aquaglyceroporin as a drug target
EC contribution
: € 885.600
Duration
: 27 months
Starting date
: 01/01/2005
Funding scheme
: Specific Targeted Research Project
Keywords
: malaria, aquaglyceroporin, assay systems, drug development
Contract/Grant agreement number
: LSHB-CT-2004-012189
Project web-site:
http://ec.europa.eu/research/health/poverty-diseases/projects/99_en.htm

Background:

Malaria is one of the three major infectious diseases. Although the disease is prevalent in the tropics and subtropics, it has caused a global emergency. Between 300 to 400 million cases with 1 million to 2 million deaths are recorded each year. A rapidly increasing resistance to antimalarial drugs calls for focused novel strategies on combating the disease.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. MalariaPorin is an interdisciplinary project that wants to take genomic information to drug development.
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. Concurrently, the conditions for generating aquaglyceroporin inhibitory drugs are developed.
It is envisioned that MalariaPorin may become the starting point for a wider strategy to assess the role of aquaporins in pathogenic parasites, such as Toxoplasma gondii and Trypanosoma brucei and cruzi, and their potential use as drug targets.

Problem:

The P. falciparum genome project aims at the accelerated discovery of novel antimalarial drug targets. Of particular interest are proteins of unusual metabolic pathways and of the parasite/host interface for metabolite exchange and ion homeostasis. Using P. falciparum genome data, the coordinator of MalariaPorin has identified a single water/glycerol channel (aquaglyceroporin, PfAQP) to be present at the parasite/host interface. It is furthermore the only member of the aquaporin family encoded in the P. falciparum genome. The PfAQP protein belongs to the major facilitator super family for nutrients and metabolites and is a bi-functional pore with high permeability for water and glycerol. Apart from PfAQP, the parasite/host interface so far consists of only five further facilitators for monocarboxylates and nucleosides. Carrying a limited interface with the least possible number of membrane channels and transporters is typical for intracellular parasites. The fact, that the aquaglyceroporin is a component of the interface strongly suggests basic functions in the parasite biochemistry.

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