Descrizione del progetto
Comunicazione fra cellule durante lo sviluppo del cervello
La comunicazione cellulare è resa possibile da molti fattori, fra cui le vescicole secrete che trasferiscono acidi nucleici, lipidi e proteine. Le vescicole extracellulari sono coinvolte nella comunicazione fra neuroni, mentre il loro ruolo nella comunicazione dei progenitori con i neuroni e i gastrociti durante lo sviluppo del cervello è stato poco studiato. In particolare, più del 60 % dei geni associati alle malattie del neurosviluppo codificano per proteine trasportate dalle vescicole extracellulari. Il progetto ExoDevo, finanziato dal CER, si propone di studiare il ruolo delle vescicole extracellulari durante lo sviluppo del cervello. Per farlo, si concentrerà sulla funzione fisiologica di tali vescicole, che mediano la segnalazione fra cellule, utilizzando la trascrittomica, la proteomica, l’imaging e l’analisi funzionale delle vescicole extracellulari provenienti da organoidi cerebrali umani. Lo studio permetterà di comprendere meglio i meccanismi fondamentali dello sviluppo cerebrale e delle patologie del neurosviluppo.
Obiettivo
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.
Campo scientifico
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-AG - HORIZON Action Grant Budget-BasedIstituzione ospitante
80539 Muenchen
Germania