Acronym: MPCM
Contract Number: LSH-CT-2006-037749
Executive Summary

Scientific Coordinator:
Giovanna CHIMINI
Université de la Méditerranée,
Centre d’Immunologie de Marseille-Luminy (CIML)
Joint Research Unit (CNRS 6102)/Inserm (U136)
Parc scientifique et Technologique de Luminiy
13009 Marseille, France
Phone : + 33 4 91 26 94 04
Fax : + 33 4 91 26 94 30
giovanna.chimini@univmed.fr

Project Manager :
Céline Damon
Université de la Méditerranée
Cellule Europe
Jardins du Pharo,
58 bd Charles Livon
13007 Marseille
Phone : + 33 4 91 69 89 10
Fax : + 33 4 91 39 66 67
celine.damon@univmed.fr

List of partners

Part n°	Organisation name	Short name	Scientific leader	Town	Country	
1 (c)	Université         de         la Méditerranée	UnivMed	Dr. G. Chimini Prof. G. Grau	Marseille	France	
2	University of Malawi	MLW	Dr.                M.E Molyneux	Blantyre	Malawi	
3	University of Douala	UDouala	Dr. I. Gouado	Douala	Cameroon	
4	London       School       of Tropical Medicine	LSHTM	Dr.       B.       de Souza	London	UK	
5	Institut National  de la Santé       et       de       la Recherche Médicale	INSERM	Dr. L. Rénia	Paris	France	
6	University of Geneva	UniGe	Dr. D. Burger	Geneva	Switzerland	
7	Centre  National   de  la Recherche Scientifique	CNRS	Dr. B. Ryffel	Orleans	France	
8	University of Sydney	U syd	Dr. N. Hunt	Sydney	Australia	

Project summary
Cerebral malaria (CM) remains a major problem of public health worldwide. The main reason is our insufficient knowledge on the mechanisms leading to this complication. We recently showed that the production of microparticles (MP) is dramatically elevated in patients with CM. Evidence in a murine model indicates that MP may be a pivotal element in CM pathogenesis, and in vitro data on human brain microvascular endothelial cells suggest that reducing MP production by anti-inflammatory drugs correlates with a reduced cytoadherence of parasitised erythrocytes.
Therefore the MPCM project aims to unravel the mechanisms of MP production, to delineate pharmacological ways to interfere with it, and to define the pathophysiological consequences of excessive MP production. Starting from the patient who develops CM, towards the fine composition of MP, we want to identify the molecules that are relevant to pathogenesis. Technologies implemented will include astrocytes and endothelial cell culture, flow cytometry, immunohistochemistry, membrane biology, magnetic resonance spectroscopy, neurochemistry, enzymology, proteomics and lipidomics.
To this end we have brought together clinical and research teams that work in complementary fields and have a specific approach to tackle the different questions raised. Colleagues from endemic countries, including Malawi, Cameroon, Tanzania and India play a major role in the project. Our approach presents a high degree of interdisciplinarity, for the reason that our consortium involves experts in clinical practice, immunology, pathology, pathophysiology, cell biology, biochemistry and genetics.
In each team, young researchers and students will work in close relationship with experienced researchers. A better understanding of CM pathogenesis should open new therapeutic avenues and lead to a better handling of patients, reduced malaria-associated mortality and morbidity by avoiding uncomplicated malaria to evolve in CM.