Project description DEENESFRITPL 3D model of blood-brain barrier to study cerebral malaria pathology Malaria is a major public health concern with more than 400 000 deaths per year. Cerebral malaria (CM) is characterised by sequestration of infected red blood cells in the brain microvasculature, blood-brain barrier (BBB) disruption and brain swelling, resulting in high mortality. The EU-funded Mal3D-BBB project aims to model the human CM pathology with cutting-edge in vitro bioengineering approaches. The researchers will develop BBB models with 3D microfluidic networks that incorporate multiple cell types: brain microvascular endothelial cells, astrocytes and pericytes. The developed platform aims to recreate physiological BBB permeability rates, and will be used to understand the molecular mechanisms of BBB disruption after P. falciparum sequestration, and whether parasite and host factors synergise to increase pathology. Show the project objective Hide the project objective Objective Malaria is a major public health problem and it still causes more than 400,000 deaths per year. Cerebral malaria (CM) is one of the most serious complications, with 20% mortality rates even after administration of fast-acting antimalarials. CM pathology is characterized by sequestration of P. falciparum-infected red blood cells (iRBC) in the brain microvasculature, blood-brain barrier (BBB) disruption, and brain swelling. Our current knowledge of CM is primarly based on autopsy studies, because of the absence of suitable animal models. However, there are numerous pathogenic aspects that cannot be studied from post-mortem samples, such as disease progression. In Mal3D-BBB, we bypass these limitations by recreating the human CM pathology with cutting-edge in vitro bioengineering approaches. Rather than using 2D endothelial monolayers, we will develop BBB models with 3D tubular geometry that incorporate multiple cell types: brain microvascular endothelial cells, astrocytes and pericytes. We will mimic vessel dimensions and flow dynamics of the brain vasculature with the goal to recreate physiological BBB permeability rates. Using such technology brings a unique angle to malaria research to evaluate in a controlled and systematic way 1) the molecular mechanisms of BBB disruption after P. falciparum sequestration, and 2) whether parasite and host factors synergize to increase pathology. The findings obtained by this cutting-edge technology will be further validated in samples from CM patients, whose neurovascular pathology has been thoroughly characterized using MRI. Our interdisciplinary approach aims to provide a holistic understanding of CM malaria pathogenesis. In return, this knowledge will identify new pathways that could be counteracted to develop therapies to reduce patient mortality. In a broader context, we will build an innovative platform that captures the complex physiology of the BBB, and can be translated to the study of other neurovascular diseases. Fields of science medical and health scienceshealth sciencesinfectious diseasesmalariamedical and health scienceshealth sciencespublic healthsocial sciencessociologydemographymortalitymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2020-STG - ERC STARTING GRANTS Call for proposal ERC-2020-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator EUROPEAN MOLECULAR BIOLOGY LABORATORY Net EU contribution € 1 492 900,00 Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all EUROPEAN MOLECULAR BIOLOGY LABORATORY Germany Net EU contribution € 1 492 900,00 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
