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Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders

Descripción del proyecto

La función del proteoma extracelular en el encéfalo sano y el encéfalo autista

Estudios recientes han demostrado que la composición del líquido cefalorraquídeo y del líquido intersticial del encéfalo influye en el desarrollo encefálico y el comportamiento. Las tecnologías ómicas demostraron que estos fluidos contienen abundantes proteínas secretadas, ARN y metabolitos. El equipo del proyecto SecretAutism, financiado con fondos europeos, adoptará un enfoque sistemático para descubrir el papel de las proteínas extracelulares del encéfalo en la salud y la enfermedad. Los objetivos específicos incluyen la identificación de las proteínas del espacio extracelular que modulan el desarrollo neuronal, prestando especial atención a las proteínas de las vesículas extracelulares, cuyas mutaciones se consideran factores de alto riesgo para trastornos del espectro autista.

Objetivo

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.

Institución de acogida

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Aportación neta de la UEn
€ 1 997 729,00
Dirección
Am Campus 1
3400 Klosterneuburg
Austria

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Región
Ostösterreich Niederösterreich Wiener Umland/Nordteil
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 997 729,00

Beneficiarios (1)