TRANSARREST

Keeping gene expression in check: eliciting the role of transcription in the maintenance of genome integrity

 Coordinatore BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING 

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 Nazionalità Coordinatore Greece [EL]
 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) 2012-11-01   -   2017-10-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING

 Organization address address: Al. Fleming Street 34
city: VARI-ATHENS
postcode: 16672

contact info
Titolo: Dr.
Nome: Maria
Cognome: Fousteri
Email: send email
Telefono: +30 2109656235
Fax: +30 2109653934

EL (VARI-ATHENS) hostInstitution 1˙500˙000.00
2    BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING

 Organization address address: Al. Fleming Street 34
city: VARI-ATHENS
postcode: 16672

contact info
Titolo: Prof.
Nome: Charalambos
Cognome: Savakis
Email: send email
Telefono: 302110000000
Fax: 302110000000

EL (VARI-ATHENS) hostInstitution 1˙500˙000.00

Mappa


 Word cloud

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

function    cs    idea    transcription    integrity    related    stability    cells    genomic    genetic    transcriptional    molecular    arrest    epigenetic    active    genome    toxicity    mechanisms    inheritance    repair    cellular   

 Obiettivo del progetto (Objective)

'Genomic integrity is essential for accurate gene expression and epigenetic inheritance. On the other hand, a prolonged transcriptional arrest can challenge genome stability, contributing to genetic and epigenetic defects and the mechanisms of ageing and disease.

Here we aim to identify the molecular mechanisms that couple transcriptional arrest to chromatin alteration and repair. We wish to explore the idea that transcription suppresses cellular toxicity and preserves genetic and epigenetic inheritance.

Towards these goals our work will be focused on:

1. Deciphering the molecular events impinging on the manner cells respond when the progress of a transcribing RNA polymerase II is blocked.

2. Exploring a novel, so far unanticipated function of key players of the transcription-associated repair pathways, such as the Cockayne Syndrome (CS) proteins, not related to repair.

3. Understanding the role of transcription in chemotherapeutic-driven toxicity.

4. Investigating novel post-translational modifications of CS and determining their function.

These objectives will be addressed using advanced proteomics and genome wide technologies in combination with biochemical and cellular techniques in normal human cells and a large battery of patient-derived cell lines. Our rational is that better understanding of CS function will help reach our ultimate goal, which is to identify the regulatory cascades involved in the interplay between genomic stability and transcription. The novel key idea put forward in this proposal is that active transcription itself directly contributes to genome integrity. While the role of DNA damage-driven transcription blockage in promoting repair is well established, the protective role of active transcription in genome stability is entirely unexplored.

If successful, the proposed studies may help reveal the underlying causes of related disorders and explain their clinical features.'

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