Project description
Signalling crosstalk at the blood brain barrier and control of central nervous system inflammation
The blood-brain barrier (BBB) isolates the central nervous system (CNS) parenchyma from the peripheral circulation. However, with multiple sclerosis (MS), the inflammatory cells and plasma proteins get into the CNS and cause lesion formation as a result of abnormal BBB permeability. Funded by the Marie Sklodowska-Curie Actions programme, the EFHHBBBMS project aims to provide a deeper understanding of BBB pathophysiology, particularly in relation to MS. Previous studies have implicated the Hedgehog pathway as a regulator of BBB integrity in MS, HIV, and stroke. The current project will test the hypothesis that Desert Hedgehog-induced signalling in endothelial cells affects inflammatory lesion expansion at intercellular BBB junctions through the involvement of co-receptor Gas1, representing a new potential target for effective MS therapies.
Objective
"Being at a major turning point in my career, after a rewarding postdoctoral fellowship in the United States, I’m applying to the MSCA-IF-2017 to ensure my return to Europe as an independent researcher in neurovascular biology. I built a proposal with the purpose of providing new understanding of Blood Brain Barrier (BBB) pathophysiology, particularly in the setting of Multiple Sclerosis. My hypothesis is that Desert Hedgehog-induced autocrine signaling in endothelial cells controls inflammatory lesion expansion via the regulation of intercellular junctions at the BBB through its co-receptor Gas1, and that this pathway may represent a new target for more effective therapies to prevent relapses and progression in Multiple Sclerosis.
I choose to join the UMR Inserm U1034 to bring together my deep BBB knowledge and its unique expertise in Hedgehog signaling and vascular biology. Moreover the Bordeaux University, through its internationally recognized neuroscience campus, offers me an exceptional opportunity to develop fruitful collaborations with many distinguished researchers.
My project is voluntarily built towards the exploitation of novel dynamic in vitro/in vivo BBB models requiring original microfluidic chamber design and 2-Photon live imaging (secondment in M. Nedergaard’s laboratory, Copenhagen), in vivo explorations of yet unpublished transgenic mice using high resolution imaging tools and the development of new molecules targeting original protein-protein interactions.
As soon as I'll get exciting data, I will disseminate my work through seminars, international conferences and publications in high impact factor journals. Moreover, I will use the opportunities from both my hosting structure and Neurocampus programs to communicate to a wider audience (laboratory visits, meetings, Brain awareness week contributor). Ultimately, this fellowship will establish my emerging status of ""young leader in neurovascular biology"" with an international collaborative network.
"
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesbasic medicineneurologymultiple sclerosis
You need to log in or register to use this function
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
75654 Paris
France