METAMETA

Metastability of proteins during tumor metastasis

 Coordinatore JOHANN WOLFGANG GOETHE UNIVERSITAET FRANKFURT AM MAIN 

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 Nazionalità Coordinatore Germany [DE]
 Totale costo 1˙366˙800 €
 EC contributo 1˙366˙800 €
 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-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2013
 Periodo (anno-mese-giorno) 2013-03-01   -   2018-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    JOHANN WOLFGANG GOETHE UNIVERSITAET FRANKFURT AM MAIN

 Organization address address: GRUNEBURGPLATZ 1
city: FRANKFURT AM MAIN
postcode: 60323

contact info
Titolo: Dr.
Nome: Ramunas Martynas
Cognome: Vabulas
Email: send email
Telefono: +49 69 798 42568

DE (FRANKFURT AM MAIN) hostInstitution 1˙366˙800.00
2    JOHANN WOLFGANG GOETHE UNIVERSITAET FRANKFURT AM MAIN

 Organization address address: GRUNEBURGPLATZ 1
city: FRANKFURT AM MAIN
postcode: 60323

contact info
Titolo: Ms.
Nome: Kristina
Cognome: Wege
Email: send email
Telefono: +49 69 798 15198
Fax: +49 69 798 15007

DE (FRANKFURT AM MAIN) hostInstitution 1˙366˙800.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

chaperones    superfamily    combined    molecular    metastasis    hsp    proteins    tumor    heterogeneity    degradation    proteome   

 Obiettivo del progetto (Objective)

'Mutational heterogeneity bestows tumors with the phenotypic plasticity and adaptability required for expansion. On the other hand, mutations destabilize proteins – lower stability (metastability) of the tumor proteome must be the inevitable consequence. We set out to systematically investigate this biochemical aspect of metastasis aiming to uncover and therapeutically exploit specific vulnerabilities resulting from protein destabilization. We will approach this goal by cataloging associations between metastasis-promoting proteins and molecular chaperones. Chaperones are obvious candidates to stabilize the proteome, therefore we will prepare a BAC-based mouse model of metastasis, where the contribution of 63 chaperones, comprising the entire murine HSP70 superfamily, to metastasis development will be individually investigated. The role of metastasis-relevant chaperones at the molecular level will be elucidated using mass spectrometry, complemented by next-generation sequencing of metastatic exome. In parallel, a novel proteomics-based method to evaluate aberrant complex formation in tumor cells will be established. Because of the high heterogeneity of cancer, molecularly tailored and combined therapies are needed. To this end, we will capitalize on insights regarding the role of chaperones in metastasis by identifying proteasomal degradation activators able to support or replace the activity of individual chaperones from the HSP70 superfamily. Finally, we will validate the potential of combined, yet specific manipulation of the folding and degradation machineries to suppress metastasis development.'

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