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DDREAMM

Financiado

Dna Damage REsponse Actionabilities Maps and Mechanisms

To monitor and protect their genomes, eukaryotic cells have evolved sophisticated DNA-damage response (DDR) systems that comprise DNA repair and DNA-damage signaling processes. DDR deficiencies are associated with diverse human di... ver más

28/02/2026

ETH Zürich

9M€

Presupuesto del proyecto: 9M€

Líder del proyecto

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH No se ha especificado una descripción o un objeto social para esta compañía.

Ver 5 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-12-16

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2019-SyG: ERC Synergy Grant

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5 Participantes

ETH Zürich

4.42M€ | Lider

SIRO JAEN

253.72K€ | Participante

MEDIZINISCHE UNIVERSITAET WI...

982.64K€ | Participante

THE CHANCELLOR MASTERS AND S...

3.46M€ | Participante

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Duración del proyecto: 74 meses Fecha Inicio: 2019-12-16
Fecha Fin: 2026-02-28

Presupuesto del proyecto 9M€

Descripción del proyecto To monitor and protect their genomes, eukaryotic cells have evolved sophisticated DNA-damage response (DDR) systems that comprise DNA repair and DNA-damage signaling processes. DDR deficiencies are associated with diverse human disorders, ranging from aggressive hereditary and sporadic cancers to inherited genetic diseases. The impact of DNA repair has also recently been harnessed to treat diseases through synthetic lethal cancer treatments and CRISPR-Cas genome editing. However, the fundamental interactions between DDR pathways that underpin such therapeutic opportunities are still not well understood. Furthermore, we are only just beginning to understand how suppressive functional interactions (so-called synthetic viability) can lead to resistance to DDR-targeting therapeutics. Our proposed research will address these important issues by using cutting-edge technologies in gene editing and chemical biology, and by taking a multidisciplinary approach to create deeply integrated genetic and physical maps of DDR pathways and interactions in many human cell types. Next-generation CRISPR-Cas transcriptional genome-wide approaches will be used to uncover hypo- and hyper-morph alleles that affect cellular sensitivity to DNA-damaging agents and DDR-enzyme inhibitors, thus providing insights into DDR events and explaining human DDR-deficiency phenotypes. Mass spectrometry and in-depth mechanistic studies will establish physical interaction networks within the genetic framework and reveal the signaling logic that underpins DDR outcomes and vulnerabilities. With chemical-genetic approaches, we will develop small molecule tools to precisely interrogate DDR pathways and that could lead to new therapeutic agents. In sum, our work should provide major insights into human genome surveillance in multiple cell types, yield powerful tools to precisely control DNA repair outcomes, and speed the development of new therapies for cancer and other diseases.

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