Toxic protein aggregation in neurodegeneration

  • Description
  • Details
  • Subprojects
  • History
  • Relations
  • Publications
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Project Description:
Formation of amyloid-like protein aggregates is the hallmark of a number of neurodegenerative diseases, but how the aggregation process is linked with cytotoxicity and cell death remains unclear. The goal of this pro¬ject is to elucidate the basic mechanisms of aggregate toxicity and how it affects the biological system in its entirety. We will analyse cell culture and mouse models of Huntington’s disease, amyotrophic lateral sclero¬sis and Alzheimer’s disease using a trans-disciplinary approach combining cellular biochemistry, quantita¬tive proteomics and 3D cryo-electron tomography. The effects of aggregating protein species (APS) formed by designer proteins and authentic disease proteins will be compared to define general and disease-specific toxicity mechanisms. The main aims of this project are:1. To determine the sequence of cellular events occurring during toxic protein aggregation. Live cell imaging and single molecule fluorescence fluctuation measurements will be employed to monitor how APS evolve from diffusible oligomers to large inclusions and quantitative proteomics will define signatures for cells with different forms of aggregates.2. To identify the mechanisms of aggregation toxicity through a systematic interactome analysis of APS in cell culture and mouse brain. The cellular localization of APS and their potential association with membrane structures and cellular machinery will be determined by cryo-ET.3. To elucidate why cellular protein quality control fails in neurodegenerative disease. Specially designed proteostasis sensors will be used to monitor the status of the protein folding machinery as aggregate pathol¬ogy develops. The potentially protective pathways of inclusion body formation will be explored using cryo-ET and laser capture dissection coupled with highly sensitive proteomics.Understanding aggregation toxicity will be invaluable in developing novel therapeutic strategies for some of the most debilitating diseases of our time.
 
Project Terms:
scientific research
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Project Categories:
Natural Sciences
 
Other Information:
Fiscal Year: 2013
Project Start Date: 1 June 2013
Project End Date: 31 May 2019
Project program: FP7-IDEAS-ERC
 
Project Funding Information:
Funding Mechanism: ERC-SyG - Synergy grant
Year Funding Organization Total Funding, $
2013 European Research Council $15,319,808
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Title FY Funding
There are no results for this project in database.
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Project Title Organization FY Funding
Toxic Protein Aggregation In NeurodegenerationMax-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev2013$15,319,808
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Project number Project title Principal investigator
There are no any related projects.
Project Title: Toxic protein aggregation in neurodegeneration
Project Number: CORDIS-108649
Project web address: Follow on CORDIS
Organization: Max-Planck-Gesellschaft Zur Förderung Der Wissenschaften Ev, Germany, Dusseldorf
Principal Investigators (PI): Franz-Ulrich Hartl, DE
 
Title Journal Year Country Rel