Innovating Works

EaSYFUN

Financiado
The role of eEF1A in synapse function, maintenance, and synucleinopathy
Synucleinopathies are neurodegenerative conditions characterized by an accumulation of the protein alpha-synuclein, including Parkinson's disease and dementia with Lewy bodies. A long asymptomatic phase precedes the onset of inval... Synucleinopathies are neurodegenerative conditions characterized by an accumulation of the protein alpha-synuclein, including Parkinson's disease and dementia with Lewy bodies. A long asymptomatic phase precedes the onset of invalidating symptoms. Early diagnostics and treatments are hampered by an incomplete understanding of the pathophysiological mechanisms. The Host has recently identified the synaptic depletion of protein elongation factor 1A (eEF1A) at early stage of the disease. In EaSYFUN, the Fellow proposes to combine state of the art genome editing with transgenic murine disease model and human induced pluripotent stem cell derived neurons to unravel eEF1A function at synapses, characterize in depth its alterations in synucleinopathy, and question its pathophysiological role in the disease onset and progress. In Aim1 we shall provide a spatiotemporal map of eEF1A in neurons and its depletion in pathology. In Aim2 we will explore knock-down and rescue of eEF1A variants. We will test whether eEF1A depletion is necessary and sufficient to lead to all or some aspects of synucleinopathy. In Aim3 we will explore the functions of eEF1A variants at synapse (protein translation or degradation, regulation of synaptic vesicle cycle, spine structure) and the binding partners of eEF1A through proteomics. We will provide insights into the alterations of synaptic functions in synucleinopathy and the role of eEF1A. The applicant will benefit from established protocols by the Host and will bring new expertise to tackle eEF1A function at synapses with unprecedented resolution and to provide new therapeutic avenues for Synucleinopathy. EaSYFUN will benefit from an ongoing collaboration with Pr Jochen Herms (DZNE, Munich, Germany). The proposed work will expand the Fellow’s core scientific expertise, soft skills, and professional network to match her plans towards an independent academic research career. ver más
30/11/2024
212K€
Duración del proyecto: 30 meses Fecha Inicio: 2022-05-23
Fecha Fin: 2024-11-30

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-05-23
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
Presupuesto El presupuesto total del proyecto asciende a 212K€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5