ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation

Informacje na temat projektu

ChaperoneRegulome

Identyfikator umowy o grant: 819753

DOI

10.3030/819753

Data podpisania przez KE 21 Marca 2019

Data rozpoczęcia 1 Stycznia 2020

Data zakończenia 31 Sierpnia 2026

Finansowanie w ramach

• EXCELLENT SCIENCE - European Research Council (ERC)

Koszt całkowity

€ 1 992 500,00

Wkład UE

€ 1 992 500,00

Koordynowany przez

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)

Okres sprawozdawczy: 2024-07-01 do 2025-12-31

Podsumowanie kontekstu i ogólnych celów projektu

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.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

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.

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

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.