QUALIAGE
"Spatial protein quality control and its links to aging, proteotoxicity, and polarity"
| Coordinatore | GOETEBORGS UNIVERSITET
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Sweden [SE] |
| Totale costo | 2˙371˙262 € |
| EC contributo | 2˙371˙262 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2010-AdG_20100317 |
| Funding Scheme | ERC-AG |
| Anno di inizio | 2011 |
| Periodo (anno-mese-giorno) | 2011-06-01 - 2016-05-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
GOETEBORGS UNIVERSITET
Organization address
address: VASAPARKEN contact info |
SE (GOETEBORG) | hostInstitution | 2˙371˙262.00 |
| 2 |
GOETEBORGS UNIVERSITET
Organization address
address: VASAPARKEN contact info |
SE (GOETEBORG) | hostInstitution | 2˙371˙262.00 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (Objective)
'Propagation of a species requires periodic cell renewal to avoid clonal senescence. My laboratory has described a new mechanism for such cell renewal in yeast, in which damaged protein aggregates are transported out of the daughter buds along actin cables to preserve youthfulness. Such spatial protein quality control (SQC) is a Sir2p-dependent process and by establishing the global genetic interaction network of SIR2, we identified the polarisome as the machinery required for mitotic segregation and translocation of protein aggregates. In addition, we found that the fusion of smaller aggregates into large inclusion bodies, a process that has been suggested to reduce the toxicity of such aggregates, requires actin cables and their nucleation at the septin ring. Sir2p controls damage segregation by affecting deacetylation and the activity of the chaperonin CCT, enhancing actin folding and polymerization. Considering that CCT has been implicated in mitigating aggregation/toxicity of polyglutamine proteins, e.g. huntingtin, and that actin cables is affecting formation, fusion, and resolution of aggregates, we hypothesize that CCT deacetylation may underlie Sirt1¿s (mammalian orthologues of Sir2p) documented beneficial effects in several neurodegenerative disorders caused by proteotoxic aggregates. This project is aimed at approaching this hypothesis and to elucidate, on a genome-wide scale, how the cell tether, sort, fuse, and detoxify aggregates with the help of CCT, actin cables, and the polarity machinery. This will be accomplished by combining the power of synthetic genetic array analysis, high-content imaging, genome wide proximity ligand assays, and microfluidics. Using such approaches, the project seeks to decipher the machineries of the spatial quality control network as a means to identify new therapeutic targets that may retard or postpone the development of age-related maladies, including neurodegenerative disorders.'