Description du projet
Le rôle du protéome extracellulaire dans le cerveau sain et autistique
De récentes études ont montré que la composition du liquide céphalo-rachidien et du liquide interstitiel dans le cerveau exerce un impact sur le développement du cerveau et le comportement. Les technologies en «-omique» ont démontré que ces fluides sont riches en protéines sécrétées, en ARN et en métabolites. Le projet SecretAutism, financé par l’UE, adoptera une approche systématique pour mettre au jour le rôle des protéines cérébrales extracellulaires dans la santé et la maladie. Ses objectifs spécifiques comprennent l’identification des protéines de l’espace extracellulaire qui modulent le développement neuronal, et mettent un accent particulier sur les protéines des vésicules extracellulaires, dont les mutations sont considérées comme des facteurs de risque élevés de troubles du spectre autistique.
Objectif
Since the ancient Egyptians, the fluid in the brain has been considered a product of spirits, a pathological signature or inert liquid. Even at the turn of the 19th century, when the cerebrospinal fluid (CSF) was first described as a physiological substance, the CSF and the interstitial fluid (ISF), the fluid surrounding all the cells of the brain, were considered solely as a cushion. Only more recently studies have begun to show that the compositions of these fluids can have a marked impact on brain development and animal behaviour. A number of studies have employed omics to demonstrate that the ISF and the CSF are rich in secreted proteins, RNAs and metabolites. However, it is still unclear how these factors influence the development and the function of the brain. Here, we will take a systematic approach to advance our knowledge about the role of extracellular proteins in the brain in health and disease. Using knowhow in studying the causes of autism spectrum disorders (ASDs) my lab will study the effects of changes in the composition of the extracellular space of the brain at unprecedented resolution and scale. Specifically, we aim to 1) functionally identify proteins of the extracellular space that modulate neural development; 2) study proteins that are packaged into extracellular vesicles and whose mutations are considered high ASD-risk factors; 3) analyse -in vivo- the function of HNRNP U, an RNA-binding protein, which we identified in brain extracellular vesicles and whose mutations are tightly linked to neurodevelopmental disorders. This endeavour will represent an important step toward a better understanding of the role of extracellular factors in brain development and function. My work will highlight an entire class of protein encoding genes that crucially contribute to neural development by a previously underappreciated pathway, i.e. through the extracellular parenchyma and that when altered lead to forms of ASDs which may be more amenable to treatment.
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
3400 Klosterneuburg
Autriche