Opis projektu
Rola proteomu zewnątrzkomórkowego w zdrowym i autystycznym mózgu
Ostatnie badania wykazały, że składy płynu mózgowo-rdzeniowego i płynu śródmiąższowego w mózgu mają wpływ na rozwój mózgu i zachowanie. Technologie omiczne wykazały, że płyny te są bogate w wydzielane białka, RNA i metabolity. W tym kontekście zespół finansowanego przez UE projektu SecretAutism zastosuje systematyczne podejście w celu odkrycia roli pozakomórkowych białek mózgu w zdrowym i chorym organizmie. Cele szczegółowe projektu obejmują ustalenie białek w przestrzeni pozakomórkowej modulujących rozwój neuronów ze szczególnym uwzględnieniem białek w pęcherzykach pozakomórkowych, których mutacje są uznawane za czynniki wysokiego ryzyka wystąpienia zaburzeń ze spektrum autyzmu.
Cel
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.
Dziedzina nauki
Program(-y)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Temat(-y)
System finansowania
HORIZON-AG - HORIZON Action Grant Budget-BasedInstytucja przyjmująca
3400 Klosterneuburg
Austria