Objective Migraine is a major disease burden on society but remains poorly understood. The onset of migraine with aura has been linked to cortical spreading depolarisation (CSD) and Professor Turgay Dalkara (the supervisor) found that inducing CSD in animal models led neurons to release inflammatory proteins in extracellular vesicles (EVs). Because brain-derived (BD)EVs cross the blood-brain barrier and their composition reflects their cellular and temporal origin, they represent biomarkers that, if isolated from the peripheral blood of migraine patients, could give an unparalleled insight into cell-specific neuroinflammation in migraine. However, current methods to isolate cell type-specific BDEVs from the blood insufficiently distinguish them from EVs of other tissues, obscuring crucial insights into cell-specific processes. Here, I (Adam Bennett, the researcher) will develop a workflow to isolate cell type-specific BDEVs from the blood of migraine patients then temporally characterise them to gain a cell-type specific molecular signature during migraine with aura. This will firstly involve the optimisation and validation of isolating neuron, astrocyte and microglia EVs (using a panel of specific markers) from the brains and peripheral blood of rats. Secondly, cell type-specific EVs isolated at different time points post-CSD evocation in rats will be characterised using proteomics to generate temporal cell type-specific data on the pathological processes post-CSD. Thirdly, with optimised time points, cell type-specific EVs will be isolated from the blood of patients after migraine with aura onset and characterised. In doing so, I will (1) identify previously unknown biomarkers to deepen our understanding of migraine with aura, with possible treatment derivations; (2) create a tool for researchers to investigate other neurological conditions through analysing cell type-specific BDEVs; (3) develop my skillset, publication record, visibility and networks to advance my career. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencescell biology Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-AG-UN - HORIZON Unit Grant Coordinator HACETTEPE UNIVERSITESI Net EU contribution € 148 478,40 Address HACETTEPE UNIVERSITESI BEYTEPE KAMPUSU REKTORLUK BINASI 06800 Cankaya Ankara Türkiye See on map Region Batı Anadolu Ankara Ankara Activity type Higher or Secondary Education Establishments 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 Total cost No data
