Extracellular vesicle-mediated cross-talk during human brain development and disease

Title Extracellular vesicle-mediated cross-talk during human brain development and disease
Acronym ExoDevo
Website https://www.psych.mpg.de/cappello
Start date 2022-10-01
End date 2027-09-30
Sponsor European Research Council - Consolidator Grant (ERC-CoG)
Institution Max Planck Institute of Psychiatry

Associated cell lines

Project Description

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 secreted vesicles 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 neurological and psychiatric diseases. With ExoDevo, I will investigate the role of EVs during brain development and identify new cell non-autonomous mechanisms underlying neurodevelopmental disorders. To achieve this aim, 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 neurodevelopmental disorders 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 neurodevelopmental disorders.