ERC Advanced Grant

Lydia Sorokin studies extracellular matrix (ECM) of blood vessels, in particular blood vessels of the brain. These vessels are particularly impermeable for cells, toxins and pathogens and together with their ECM constitute the blood-brain barrier (BBB). One of the main working models in Lydia Sorokin's lab deals with multiple sclerosis and how leukocytes ("white blood corpuscles") migrate across the BBB into the brain to induce disease symptoms. The focus in the ERC project is on the particular space - discovered by the Sorokin team - that is unique for cerebral blood vessels and is formed by two specialized ECM structures that constitute the borders of the perivascular space. This site harbours genetically distinct resident leukocyte populations, the function of which are unknown. In addition, it is a preferred location for leukocytes before they penetrate the brain in inflammatory diseases of the brain. The aim of the project - financed by the ERC Grant - is to study the molecular processes that are not only essential for maintaining the BBB, but which also make it possible for the immune cells to penetrate this barrier. To this end, Lydia Sorokin and her team aim to create three-dimensional simulations of the essential components of the BBB in vitro (in the laboratory) including the perivascular space. In combination with studies involving genetically modified mice, the researchers want to find out how, in the case of inflammatory diseases, the leukocytes manage to penetrate into the brain. Simulating the BBB in the lab will in the future open possibilities for screening of drug transport into the brain to combat inflammation or even tumours in the brain.