ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation

Projektinformationen

ChaperoneRegulome

ID Finanzhilfevereinbarung: 819753

DOI

10.3030/819753

EK-Unterschriftsdatum 21 März 2019

Startdatum 1 Januar 2020

Enddatum 31 August 2026

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 992 500,00

EU-Beitrag

€ 1 992 500,00

Koordiniert durch

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)

Berichtszeitraum: 2024-07-01 bis 2025-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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.