Descripción del proyecto
Comunicación intercelular durante el desarrollo del encéfalo
La comunicación celular depende de numerosos factores, como las vesículas secretadas que transfieren ácidos nucleicos, lípidos y proteínas. Las vesículas extracelulares (VE) participan en la comunicación entre neuronas, aunque su participación en la comunicación de las células progenitoras con las neuronas y los astrocitos durante el desarrollo del encéfalo apenas se ha investigado. Cabe destacar que más del 60 % de los genes asociados con enfermedades del neurodesarrollo codifican proteínas transportadas por VE. El objetivo del proyecto ExoDevo, financiado por el nsejo Europeo de Investigación, es estudiar la función de las VE durante el desarrollo del encéfalo. Se centrará en la función fisiológica de las VE, mediante la señalización intercelular, utilizando la transcriptómica, la proteómica, la imagenología y el análisis funcional de VE de organoides encefálicos humanos. Este estudio permitirá comprender mejor los mecanismos fundamentales del desarrollo del encéfalo y las enfermedades del neurodesarrollo.
Objetivo
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.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
80539 Muenchen
Alemania