Descrizione del progetto
Ruolo del proteoma extracellulare nel cervello sano e nel cervello autistico
Alcuni studi recenti hanno dimostrato che la composizione del liquido cerebrospinale e del liquido interstiziale nel cervello incide sullo sviluppo cerebrale e sul comportamento. Le tecnologie omiche hanno evidenziato che questi liquidi sono ricchi di proteine, RNA e metaboliti secreti. Il progetto SecretAutism, finanziato dall’UE, adotterà un approccio sistematico per rivelare il ruolo delle proteine extracellulari del cervello in condizioni di salute e di malattia. Tra gli obiettivi specifici vi è l’identificazione delle proteine dello spazio extracellulare che modulano lo sviluppo neurale, prestando particolare attenzione alle proteine nelle vescicole extracellulari, le cui mutazioni sono considerate fattori di rischio elevati per i disturbi dello spettro autistico.
Obiettivo
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.
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
3400 Klosterneuburg
Austria