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Proteomics 4D: The proteome in context

Descrizione del progetto

Analisi proteomica dei moduli multiproteici

Le proteine cellulari sono disposte in una rete costituita da moduli multiproteici interconnessi che svolgono un ruolo cruciale nella formazione dei fenotipi complessi. Gli approcci proteomici si sono finora concentrati sull’identificazione e la quantificazione di un gran numero di proteine come entità indipendenti. Il progetto PROTEOMICS4D, finanziato dall’UE, propone invece di analizzare i moduli proteici, con l’auspicio di fornire nuovi spunti e opportunità per scoprire l’intricata relazione tra fattori genetici e fenotipi delle malattie. Il lavoro si concentrerà sui moduli delle proteine chinasi, a causa della loro connessione riconosciuta con il cancro. Successivamente, il progetto intende sviluppare una piattaforma più versatile per svelare l’impatto delle mutazioni associate alle malattie sull’organizzazione del proteoma e sullo sviluppo di malattie complesse.

Obiettivo

Elements operating in the context of a system generate results that are different from the simple addition of the results of each element. This notion is one of the basic tenants of systems science. In systems biology/medicine complex (disease) phenotypes arise from multiple interacting factors, specifically proteins. Yet, the biochemical and mechanistic base of complex phenotypes remain elusive.
An array of powerful genomic technologies including GWAS, WGS, transcriptomics, epigenetic analyses and proteomics have identified numerous factors that contribute to complex phenotypes. It can be expected that over the next few years, genetic factors contributing to specific complex phenotypes will be comprehensively identified, while their interactions will remain elusive.
The project “Proteomics 4D: The proteome in context “explores the concept, that complex phenotypes arise from the perturbation of modules of interacting proteins and that these modules integrate seemingly independent genomic variants into a single biochemical response. We will develop and apply a generic technology to directly measure the composition, topology and structure of wild type and genetically perturbed protein modules and relate structural changes to their functional output.
This will be achieved by a the integration of quantitative proteomic and phosphoproteomic technologies determining molecular phenotypes, and hybrid structural methods consisting of chemical cross-linking and mass spectrometry, cryoEM and computational data integration to probe structural perturbations.
The project will focus initially on the structural and functional effects of cancer associated mutations in protein kinase modules and then generalize to study perturbed modules in any tissue and disease state. The resources supporting this technology will be disseminated to catalyze a broad transformation of biology and molecular medicine towards the analysis of the proteome as a modular entity, the proteome in context.

Meccanismo di finanziamento

ERC-ADG - Advanced Grant

Istituzione ospitante

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Contribution nette de l'UE
€ 2 208 150,00
Indirizzo
Raemistrasse 101
8092 Zuerich
Svizzera

Mostra sulla mappa

Regione
Schweiz/Suisse/Svizzera Zürich Zürich
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 2 208 150,00

Beneficiari (1)