Project description
Cell to cell communication during brain development
Cellular communication is enabled by many factors including secreted vesicles that transfer nucleic acids, lipids, and proteins. Extracellular vesicles (EVs) are involved in neuron-to-neuron communication, while EV's role in the progenitor-to-neuron and -astrocyte communication during brain development has been poorly investigated. Notably, more than 60% of the genes associated with neurodevelopmental diseases encode proteins carried by EVs. The ERC-funded ExoDevo project aims to investigate the role of EVs during brain development. It will focus on the physiological function of EVs, mediating the cell-to-cell signalling, using transcriptomics, proteomics, imaging, and functional analysis of EVs from human cerebral organoids. This study will provide a better understanding of the fundamental mechanisms in brain development and neurodevelopmental pathologies.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
80539 Muenchen
Germany