Project description
Role of the extracellular proteome in healthy and autistic brain
Recent studies have shown that the compositions of cerebrospinal fluid and interstitial fluid in the brain have an impact on brain development and behaviour. Omics technologies demonstrated that these fluids are rich in secreted proteins, RNAs and metabolites. The EU-funded SecretAutism project will take a systematic approach to uncover the role of extracellular brain proteins in health and disease. Specific objectives include the identification of the extracellular space proteins that modulate neural development with a particular focus on the proteins in extracellular vesicles, whose mutations are considered high autism spectrum disorders risk factors.
Objective
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.
Fields of science
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-AG - HORIZON Action Grant Budget-BasedHost institution
3400 Klosterneuburg
Austria