FOLDEGProject reference: 303096
Funded under :
Defining the pathways and mechanism of misfolded protein triage and quality control in eukaryotic cells
Total cost:EUR 263 660,7
EU contribution:EUR 263 660,7
Topic(s):FP7-PEOPLE-2011-IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2011-IOFSee other projects for this call
Funding scheme:MC-IOF - International Outgoing Fellowships (IOF)
Proteins need to be correctly folded to carry out their biological function. Failure to fold leads to aberrant protein conformations that have an increased tendency to aggregate and have deleterious effect on cell viability. Eukaryotes have developed a sophisticated protein quality control (QC) system that protects cells from misfolded or incompletely synthesized polypeptides that would otherwise interfere with normal cellular functions or even induce cellular death. The QC system may promote refolding of these non-native proteins by molecular chaperones, enhance their degradation by the ubiquitin-proteasome system or autophagy, or terminally sequester these misfolded proteins in inclusion bodies called IPODs. Impairment of the activity of this QC system, for instance due to ageing or disease, is thought to underlie the growing number of age-related aggregation disorders, such as Parkinson, Alzheimer and Huntington disease, all of which are characterized by accumulation of misfolded aggregated proteins. At present, it remains largely elusive how the quality control machinery recognizes misfolded proteins, and how the triage decision is implemented: i.e. why certain misfolded proteins are refolded whereas others are targeted for degradation or sequestered in cellular inclusions. The goal of this project is therefore to identify the played of the QC machinery and define how the interplay between molecular chaperones and degradation pathways maintain cellar protein homeostasis. The proposed work will build on the large body of work of the host laboratories and will combine systems approaches with cell biology and biochemistry to address these important questions.
EU contribution: EUR 263 660,7
3584 CS UTRECHT