Decoding the DNA damage signalling in C. elegans by proteomic analyses of ADP-ribosylation

Información del proyecto

InVivo_DDR_ADPR

Identificador del acuerdo de subvención: 657501

DOI

10.3030/657501

Proyecto cerrado

Fecha de la firma de la CE 8 Abril 2015

Fecha de inicio 1 Abril 2016

Fecha de finalización 31 Marzo 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 159 460,80

Aportación de la UE

€ 159 460,80

Coordinado por

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany

Objetivo

Preservation of genome integrity and stability is critical for survival and propagation of individuals and species. Organisms have thus evolved rapid and efficient mechanisms -collectively termed the DNA damage response (DDR)- to combat threats posed by DNA damage. Among these, the post-translational modification (PTM) ADP-ribosylation (ADPR) plays a decisive role in effective DDR. Although much is known about the relevance of ADPR upon DNA injury, the underlying molecular mechanisms are still poorly understood and no systematic, unbiased proteome-wide study to determine ADPR targets in vivo has been conducted to date. The most challenging and innovative goal of this proposal is to profile in vivo ADP-ribosylated peptides during DDR in the well-established model system Caenorhabditis elegans by the combined application of advanced proteomic approaches. I will develop novel enrichment strategies that will allow me to confidently map for the first time all the sites of ADPR throughout the C. elegans proteome. I will take advantage of SILAN technology, which allows stable isotope labelling in C. elegans, to determine the quantitative profiles of thousands of ADPR sites during DDR. By bioinformatic analysis, I will select candidate proteins for further investigation of the biological role of DNA damage-induced ADPR. I will then test the biological impact of ADPR of these candidates through site-specific mutation of their identified modification sites. Finally, I will perform biochemical, molecular and functional experiments to study how ADPR alters the activity of these proteins and thereby characterize the mode of ADPR action. Understanding the regulatory networks that underlie such a complex biological process at the organism level will provide new insights for improved treatment of DNA damage-related diseases including cancer. This is an ambitious, innovative, cross-disciplinary project at the forefront of two exciting fields, biology and proteomics.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › medicina clínica › oncología › cáncer de próstata
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas › proteómica
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › ácido nucleico
• ciencias naturales › ciencias biológicas › genética › ADN
• ciencias naturales › ciencias químicas › química orgánica › aminas

Palabras clave

• ADP-ribosylation
• C. elegans

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2014

Coordinador

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

• Aportación neta de la UEn: € 159 460,80
• Dirección: HOFGARTENSTRASSE 8 ; 80539 Munchen ; Alemania
• Región: Bayern › Oberbayern › München, Kreisfreie Stadt
• Tipo de actividad: Research Organisations
• Coste total: € 159 460,80