B3M
Financiado
Breaking into the brain- basement membranes and the perivascular niche
In neuroinflammation leukocytes reside for several days in the perivascular niche of cerebral blood vessels - defined by the basal surface of the endothelium, the endothelial basement membrane (BM) and an outer parenchymal BM with...
In neuroinflammation leukocytes reside for several days in the perivascular niche of cerebral blood vessels - defined by the basal surface of the endothelium, the endothelial basement membrane (BM) and an outer parenchymal BM with associated astrocyte endfeet (Fig. 1) - a poorly studied site but of utmost fundamental and clinical relevance. This site is also emerging as harbouring genetically distinct resident cell populations, the function of which are unclear. BMs define the perivascular niche and the sealed nature of this compartment in an unknown manner. B3M will explore the perivascular niche of cerebral vessels. Using our new dextran-hydrogel with tuneable adhesive, stiffness and degradability properties and cerebral endothelial cells derived from induced pluripotent stem cells (iPSC) we will recreate the subendothelial site; we will sequentially increase its complexity to reflect the in vivo spatial arrangement of cells and BMs, within the most correctly mimicked environmental properties, in a system that permits perfusion with immune cells and live imaging. Parallel ex vivo and synthetic approaches will further break down the complexity of this site into discrete steps and using multiscale imaging of new split-cre transgenic mice we will track, target and profile perivascular cells lacking BM receptors. Studies to date on leukocyte entry into the brain focus on endothelial properties or immune cell behaviour with little consideration of the 3D relationship between cellular and BM barriers and their functional interdependence. My unique knowledge on extracellular matrix structure/function of cerebral vessels and leukocyte migration into the brain, allows me to identify key elements of the perivascular niche and how they can be mimicked in vitro and targeted in vivo. B3M’s cross-disciplinary approach will decipher cellular and molecular events occurring after leukocyte penetration of the endothelium in the perivascular niche, shedding light on a black box.
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Duración del proyecto: 59 meses
Fecha Inicio: 2022-08-01
Fecha Fin: 2027-07-31
Fecha Fin: 2027-07-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-08-01
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2021-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 3 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
UNIVERSITAET MUENSTER
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5