CTCF control of genome stability in ageing

Projektinformationen

CTCFStableGenome

ID Finanzhilfevereinbarung: 788937

DOI 10.3030/788937

EK-Unterschriftsdatum 25 Juni 2018

Startdatum 1 September 2019

Enddatum 31 August 2024

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 2 488 251,00

EU-Beitrag € 2 488 251,00

Koordiniert durch

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

Ziel

. Genome stability is one of the most important features in maintaining tissue homeostasis throughout the human lifespan. The research presented here will dissect how the insulator protein CCCTC-binding factor (CTCF), a ubiquitous 11 zinc finger transcription factor, controls the stability of the mammalian genome during ageing.
. In Aim 1, we will elucidate how CTCF and tissue-specific master regulators maintain the functional stability of the genome during healthy ageing by developing a novel protocol to map simultaneously transcription and open chromatin in isolated hepatocyte nuclei. Using this protocol, we will explore how CTCF binding stabilizes cellular homeostasis during ageing by knocking down CTCF in vivo, both in isolation and simultaneously with knock down of liver-specific master regulators.
. In Aim 2, we will reveal the molecular mechanisms underlying CTCF binding sites as susceptibility loci for somatic mutations. We will profile the mutations in open chromatin of single nuclei immediately following acute exposure to a chemical mutagen; comparing how the pattern of mutations in CTCF bound regions changes across an allelic series of CTCF knockdown mice will reveal how CTCF binding shapes the stability of the genome towards mutations.
. These integrated strategies develop and deploy powerful, cutting-edge experimental approaches to reveal novel aspects of how CTCF binding stabilises the mammalian genome during healthy ageing as well as during mutagenesis.

Wissenschaftliches Gebiet

• natural sciences › chemical sciences › inorganic chemistry › transition metals
• natural sciences › biological sciences › cell biology
• natural sciences › biological sciences › genetics › mutation
• natural sciences › biological sciences › genetics › genomes
• medical and health sciences › basic medicine › physiology › homeostasis

Schlüsselbegriffe

• Ageing
• Evolution
• Insulator
• Transcription
• Epigenetics
• Genome regulation
• Mutagenesis
• Regulatory networks

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-2017-ADG - ERC Advanced Grant

Aufforderung zur Vorschlagseinreichung

ERC-2017-ADG

Finanzierungsplan

ERC-ADG - Advanced Grant

Gastgebende Einrichtung

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

• Netto-EU-Beitrag: € 2 488 251,00
• Adresse: IM NEUENHEIMER FELD 280 ; 69120 Heidelberg ; Deutschland
• Region: Baden-Württemberg › Karlsruhe › Heidelberg, Stadtkreis
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 2 488 251,00

Begünstigte (1)

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Deutschland

• Netto-EU-Beitrag: € 2 488 251,00
• Adresse: IM NEUENHEIMER FELD 280 ; 69120 Heidelberg
• Region: Baden-Württemberg › Karlsruhe › Heidelberg, Stadtkreis
• Aktivitätstyp: Research Organisations
• Gesamtkosten: € 2 488 251,00