Description du projet
Un modèle de poisson zèbre de la barrière hémato-encéphalique
La barrière hémato-encéphalique (BHE) est essentielle à l’homéostasie cérébrale, car elle définit le transit moléculaire et cellulaire entre le cerveau et le système circulatoire. Pour ce faire, elle utilise des communications complexes entre les cellules endothéliales et d’autres composants du système neurovasculaire. Pour étudier la perméabilité de la BHE, le projet Ctrl-BBB financé par l’UE utilisera le modèle du poisson zèbre en raison de sa nature transparente et de sa capacité à subir des analyses génétiques non invasives. Étant donné que la BHE interdit la libération de médicaments dans le SNC, comprendre comment il est régulé permettra de révéler de nouvelles voies thérapeutiques pour différents troubles, notamment l’AVC, la sclérose en plaques et la neurodégénérescence.
Objectif
Brain endothelial cells (ECs) are endowed with a set of molecular and metabolic adaptations that stringently orchestrate the molecular and cellular transit between the brain and the circulatory system. These adaptations constitute the blood-brain barrier (BBB) and are pivotal to brain homeostasis and protection. Accordingly, BBB dysfunction is a unifying hallmark of many cerebrovascular diseases, including stroke, multiple sclerosis and neurodegeneration. Healing the BBB to treat to the brain is therefore emerging as a powerful therapeutic avenue for a spectrum of human CNS disorders. In addition, through its neuroprotective function, the BBB represents the main obstacle for CNS drug delivery. There is consequently an urgent need to identify methods to control BBB in health and disease. Of pivotal importance, BBB is not genetically hardwired, but instead results from ongoing neurovascular communications taking place between the ECs and the other components of the neurovascular unit. Shedding light on these communications, and raising our understanding to the mechanistic level will undoubtedly yield transformative therapeutic strategies for human brain disorders. A key obstacle in the study of BBB permeability resides in its complex regulation across cells and tissues. This complexity cannot be recapitulated in cell culture experiments. Our laboratory has recently identified and validated the transparent zebrafish as ideally suited to facilitate these studies, by empowering non-invasive genetic analyses of BBB function under normoxia. Together with a conserved BBB genetic instruction program, the zebrafish cerebrovasculature qualifies as a an alternative “miniature BBB model” where neurovascular communication can be studied at an unprecedented pace. Ctrl-BBB will pioneer synergistic approaches between the zebrafish and the mouse model, to bring BBB research in the era of highly parallel genetic approaches and BBB-focused therapeutic strategies for brain disorders.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
1050 Bruxelles / Brussel
Belgique