TRNAMODI

The in vivo roles of tRNA modification

 Coordinatore MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V. 

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 Nazionalità Coordinatore Germany [DE]
 Totale costo 1˙500˙000 €
 EC contributo 1˙500˙000 €
 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 2012
 Periodo (anno-mese-giorno) 2012-12-01   -   2017-11-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.

 Organization address address: Hofgartenstrasse 8
city: MUENCHEN
postcode: 80539

contact info
Titolo: Dr.
Nome: Sebastian
Cognome: Leidel
Email: send email
Telefono: +49 251 8346894
Fax: +49 251 8346900

DE (MUENCHEN) hostInstitution 1˙500˙000.00
2    MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.

 Organization address address: Hofgartenstrasse 8
city: MUENCHEN
postcode: 80539

contact info
Titolo: Ms.
Nome: Yvonne
Cognome: Wilken
Email: send email
Telefono: +49 251 70365902
Fax: +49 251 70365999

DE (MUENCHEN) hostInstitution 1˙500˙000.00

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modifications    trna    ms    rna    cellular    evolution    mass    spectrometry    link    function    translation    modification    protein    first    sequence    vivo    phenotypes    quantitative   

 Obiettivo del progetto (Objective)

'tRNA molecules are key in translating the genetic information into a protein sequence and critical for all aspects of cellular metabolism. Interestingly, tRNAs carry a plethora of chemical modifications, thought to regulate their function. Many of these modifications are evolutionarily highly conserved, and some linked to human degenerative diseases and cancer. However, we know little about their in vivo function and the mechanisms of how aberrations in tRNA modification lead to cellular phenotypes. Thus, my proposal aims at gaining mechanistic insights into the in vivo function of tRNA modifications by performing a comprehensive systems analysis of tRNA modification pathways in yeast: First, I will identify transcripts, which are abnormally translated in tRNA modification mutants, thus causing the observed phenotypes. Importantly, I will define the codon signatures that are the underlying cause. Second, I will develop a mass spectrometric LC-MS/MS-based workflow, allowing for a quantitative and sequence specific analysis of RNA modifications, which is currently not done in Europe. Third, by combining population analyses and long-term evolution experiments, I will address how tRNA modifications constrain the evolution of genomes and modulate cellular stress responses. To achieve my goals, I will combine novel technologies and genetics in an unprecedented manner to push the limits of our understanding. I will employ ribosome profiling, a novel method, that provides high-resolution snapshots of the translatome. I will use quantitative RNA mass spectrometry to establish the link between tRNA modification and changes in translation. Finally, I will use quantitative protein mass spectrometry to verify the translation effects of tRNA hypomodification at the proteome level. Taken together, my project will for the first time unbiasedly link tRNA modifications and translation in vivo by a systems approach and provide an important service to the European RNA community.'

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Invariant Representations for High-Dimensional Signal Classifications

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ROBUSTFINMATH (2014)

Robust Financial Mathematics: model-ambiguous framework for valuation and risk management

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SCADAPT (2012)

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