ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation

Información del proyecto

ChaperoneRegulome

Identificador del acuerdo de subvención: 819753

DOI

10.3030/819753

Fecha de la firma de la CE 21 Marzo 2019

Fecha de inicio 1 Enero 2020

Fecha de finalización 31 Agosto 2026

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 992 500,00

Aportación de la UE

€ 1 992 500,00

Coordinado por

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Periodic Reporting for period 4 - ChaperoneRegulome (ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation)

Período documentado: 2024-07-01 hasta 2025-12-31

Resumen del contexto y de los objetivos generales del proyecto

Protein misfolding is at the heart of several diseases including neurodegeneration, which collectively affect 7 million people in Europe, costing the healthcare systems €130 billion per year. Proteins with complex primary sequences such as long stretches of glutamine (polyQ), adopt non-native conformations and aggregate. The disease-causing protein may be expressed at equal levels in a variety of tissues, yet misfolding occurs only in few cell-types – in most cases neurons. Defining the relevant cellular context that impacts tissue-specific manifestation of protein misfolding is of paramount importance to address the basis of neurodegeneration paving avenues for therapeutic intervention. Novel therapies will then help us to tackle/ mitigate the age-related health concerns faced by the Western society.
The overall objective of this project is to identify why neurons are susceptible to protein misfolding diseases. We will address this objective by combining new animal models and cell cultures, along with state-of-the-art genomic technologies.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

In order to identify the determinants within neurons that make them susceptible to misfolding diseases, we have to generate new mouse models. We have now generated these models and performed transcriptomics experiments to identify genes that are misregulated when misfolding happens in neurons. We have also established a few other models to study misfolding of proteins inside neurons. We do not have any concrete results yet as we are still finishing validation experiments.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

We hope to identify novel mechanisms that underlie suscpetibility of neurons to protein misfolding diseases. We will validate these mechanisms in cell cultures and in mouse brains. Molecular mechanisms will pave new avenues for novel therapeutics to treat neurodegenerative diseases.