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HEDoctoral network2023–2026

Chrom_rare · Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-01-01 → 2026-12-31
EU contribution
€2,357,093
Participants
15
Scheme
HORIZON-TMA-MSCA-DN

Lines connect the coordinator with its partners.

Results in brief

Unveiling the molecular basis of chromatinopathies to delineate innovative therapeutic solutions

Understanding and Addressing Chromatinopathies: A Step Toward Better Diagnosis and Treatment Chromatinopathies (CPs) are a group of rare genetic disorders caused by mutations in genes that regulate how DNA is organized and accessed within our cells. These mutations disrupt gene function, leading to a range of clinical symptoms shared across different CPs. Some well-known conditions within this group include Kabuki Syndrome (KS), CHARGE Syndrome (CS), Rubinstein-Taybi Syndrome (RTS), and Cornelia de Lange Syndrome (CdLS). Although scientists have identified the genes responsible for these disorders, we still lack a full understanding of how their inactivation affects cellular functions and leads to disease. The symptoms of CPs vary significantly from patient to patient, suggesting that genetic mutations alone may not explain the full picture. Other factors—such as epigenetic changes (which influence how genes are turned on or off) and interactions with environmental or additional genetic factors—could play a role in disease development and severity. This knowledge gap presents an urgent medical need: understanding the genetic and epigenetic mechanisms behind CPs is crucial for developing better diagnostic tools and potential treatments. Through Chrom_Rare, we aim to bridge this gap by training the next generation of researchers with expertise in chromatin biology, advanced molecular techniques, and computational analysis. Our project will also work to translate scientific discoveries into practical solutions for patients. Our approach includes: Developing disease models that mimic key clinical features of CPs (WP1) Investigating the genetic, epigenetic, and structural factors contributing to CPs (WP2) Identifying disrupted regulatory mechanisms that could be targeted for therapy (WP3) By addressing these critical scientific, medical, and socio-economic challenges, Chrom_Rare strives to pave the way for better understanding and treatment of chromatinopathies, ultimately improving the lives of affected individuals and their families.

Data: CORDIS, © European Union

Project objective

Chromatinopathies (CPs) are a group of rare genetic diseases, which share clinical features as well as causal genetic alterations, leading to the inactivation of chromatin regulators involved in gene expression control and 3D chromatin organization. Within the framework of Chrom_Rare, we will focus on a group of clinically well-defined CPs, including Kabuki Syndrome, Charge Syndrome, Rubinstein-Taybi Syndrome and Cornelia de Lange Syndrome. Although the causative genes for these CPs have been identified, the consequences of their inactivation both at the molecular and functional level, have not been defined. The clinical features of CPs vary widely, suggesting that the impact of the haploinsufficiency of the affected chromatin regulators could depend on the epigenetic state and/or interactions with additional genetic and environmental factors. Hence understanding the genetic and epigenetic determinants of CPs represent an immediate medical need, as this will ultimately facilitate reaching the development of new therapeutic approaches. Our main goal is to set-up an intra-sectoral, cross-disciplinary training programme that would prepare the next generation of researchers equipped with advanced theoretical, technical and computational skills to study fundamental aspects of chromatin biology and their impact on CPs. In parallel, Chrom_Rare will devise new strategies to translate the molecular findings into new diagnostic and therapeutic approaches for patients affected by CPs. To enable understanding the molecular basis of chromatinopathies, we aim at developing multiple disease models recapitulating the main clinical features of CPs (WP1), investigating the genetic, epigenetic and topological determinants of CPs (WP2) and uncovering perturbed regulatory circuitries suitable for therapeutic intervention (WP3). Overall Chrom_rare will address unmet socio-economic, medical and scientific needs, for the understanding and possible treatment for CPs.

Original text from CORDIS.

Participants

  • UNIVERSITA DEGLI STUDI DI TRENTO · TrentoCoordinatorItaly
  • AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MadridSpain
  • Association Syndrome Kabuki · Milizac-GuipronvelFrance
  • Associazione Italiana Sindrome KabukiItaly
  • BIOTALENTUM TUDASFEJLESZTO KFT · GoedoelloHungary
  • CENTRE HOSPITALIER UNIVERSITAIRE MONTPELLIER · MontpellierFrance
  • EVOTEC INTERNATIONAL GMBH · HamburgGermany
  • GENEXPLAIN GMBH · WolfenbuttelGermany
  • INSTYTUT BIOLOGII DOSWIADCZALNEJ IM. M. NENCKIEGO POLSKIEJ AKADEMII NAUK · WarszawaPoland
  • ISTITUTO AUXOLOGICO ITALIANO · MILANOItaly
  • STICHTING RADBOUD UNIVERSITEIT · NijmegenNetherlands
  • THE UNIVERSITY OF MANCHESTER · ManchesterUnited Kingdom
  • UNIVERSIDAD DE CANTABRIA · SANTANDERSpain
  • UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II · NapoliItaly
  • UNIVERSITE DE MONTPELLIER · MontpellierFrance

Links

Data: CORDIS, © European Union