Description du projet
La communication intercellulaire au cours du développement du cerveau
La communication cellulaire est assurée par de nombreux éléments, notamment des vésicules sécrétées qui transfèrent des acides nucléiques, des lipides et des protéines. Les vésicules extracellulaires (VE) sont impliquées dans la communication interneuronale, mais le rôle joué par les VE dans les communications des cellules progénitrices vers les neurones et les astrocytes au cours du développement du cerveau a été peu étudié. Il convient en particulier de noter que plus de 60 % des gènes associés aux maladies neurodéveloppementales codent des protéines transportées par les VE. Le projet ExoDevo, financé par le CER, a pour ambition d’étudier le rôle des VE au cours du développement du cerveau. Il se concentrera sur la fonction physiologique des VE, en tant que médiateurs de la signalisation intercellulaire, en ayant recours à la transcriptomique, la protéomique, l’imagerie et l’analyse fonctionnelle des VE provenant d’organoïdes cérébraux humains. Cette étude permettra de mieux comprendre les mécanismes fondamentaux du développement du cerveau et des pathologies neurodéveloppementales.
Objectif
Cellular cross-talk is an essential process influenced by numerous factors including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neuron-to-neuron communication while the role of EVs in progenitor-to-neuron and -astrocyte communication occurring during brain development has not been systematically investigated. Extracellular signals regulating the development of the brain are key players altered in many neurodevelopmental disorders (NDDs). Strikingly, we have found that more than 60% of the genes associated with NDDs encode for proteins that are loaded into EVs.
With ExoDevo, inspired by new cell-non-autonomous mechanisms that we have identified as the cause of NDDs, I will investigate the role of EVs during brain development. I will focus on the physiological function of EVs that mediate the signals for cell-to-cell cross-talk and combine transcriptomic, proteomic, imaging, and functional analysis of EVs derived from human cerebral organoids. This will open new avenues in order to tackle fundamental questions, such as how different cells communicate and feedback at different times and distances in the highly dynamic process of brain development. Ultimately, this will be investigated in human models of NDDs and will allow me to identify pathologically altered cellular cross-talk mediated by EVs. This knowledge of the cellular processes governing EVs’ biology will provide the basis to better understand novel mechanisms underlying brain development and neurodevelopmental human pathologies and explore new deliverable compounds for therapy. My expertise in human brain development and diseases together with the possibility of combing multiple technologies will be indispensable to achieve these essential goals. Meanwhile, exploring these novel aspects of brain development will bring me beyond my current research focus and broaden my perspectives on NDDs.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitution d’accueil
80539 Muenchen
Allemagne