ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation

Informazioni relative al progetto

ChaperoneRegulome

ID dell’accordo di sovvenzione: 819753

DOI

10.3030/819753

Data della firma CE 21 Marzo 2019

Data di avvio 1 Gennaio 2020

Data di completamento 31 Agosto 2026

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 992 500,00

Contributo UE

€ 1 992 500,00

Coordinato da

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)

Periodo di rendicontazione: 2024-07-01 al 2025-12-31

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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.