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HEDoctoral network2023–2027

CohesiNet · Cohesin and its regulators: from chromosome dynamics and nuclear architecture to human diseases

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-01-01 → 2027-03-31
EU contribution
€2,649,823
Participants
22
Scheme
HORIZON-TMA-MSCA-DN

Lines connect the coordinator with its partners.

Results in brief

Cohesin and its regulators: from chromosome dynamics and nuclear architecture to human diseases

Cohesin is an evolutionarily conserved multi-protein complex that is part of the structural maintenance of chromosomes protein family. It is capable of topologically entrapping DNA molecules, thereby mediating sister chromatid cohesion—an essential function for the accurate segregation of chromosomes, as well as for DNA replication and repair. Recent discoveries have revealed that cohesin can also generate and maintain DNA loops through an ATPase-dependent in cis DNA tethering activity known as loop extrusion. This process is vital for organising chromatin architecture and regulating gene transcription, making it critical for cell differentiation and development. Despite these insights, the molecular mechanisms underlying cohesin's role in these key cellular processes remain poorly understood. Mutations in the genes encoding cohesin subunits and cohesin regulators give rise to a group of developmental disorders collectively referred to as “cohesinopathies” and have also been implicated in various types of cancer. However, the pathogenesis of these devastating diseases is not yet fully understood. The CohesiNet action seeks to address these unresolved questions within the field of cohesin biology through an innovative research programme. The CohesiNet consortium aims to explore the fundamental mechanisms by which cohesin functions during chromosomal cohesion and loop extrusion, to identify the regulatory modules governing cohesin activity, and to gain deeper insights into the molecular underpinnings of cohesin-related diseases. These ambitious objectives will be pursued through a combination of multi-disciplinary, hypothesis-driven, and exploratory approaches, while fostering a culture of communication and collaboration among academic and private institutions throughout the European Union. A cohort of ten PhD students will be trained within the CohesiNet consortium, engaging with these critical scientific questions. They will gain valuable skills that will enhance their career prospects, while also embracing the principles of Open Science and appreciating the importance of inclusion, transparency, accessibility, and integrity in scientific research. Additional information about the CohesiNet programme and network members can be found in the dedicated project website (https://www.cohesinet.eu/).

Data: CORDIS, © European Union

Project objective

Cohesin is an evolutionarily conserved multi-protein complex that belongs to the structural maintenance of chromosomes protein family. It can topologically entrap DNA molecules mediating sister chromatid cohesion, a function important for accurate chromosome segregation and DNA replication/repair. It has been recently discovered that cohesin can generate and maintain DNA loops by an ATPase-dependent in cis DNA tethering activity, called loop-extrusion, critical for organising chromatin architecture and regulating gene transcription, and as such thought to be important for cell differentiation and development. However, the molecular mechanisms by which the cohesin complex achieve these key cellular functions remain to be elucidated. Mutations in genes coding for cohesin and its regulators lead to a class of developmental disorders collectively called “cohesinopathies” and have been found in several types of cancer. Nonetheless, the pathogenesis of these devastating human diseases is poorly understood.CohesiNet aims to answer outstanding questions in the field of cohesin biology by a highly innovative research programme. This consortium will investigate fundamental mechanisms on how cohesin acts during chromosomal cohesion and loop extrusion, identify regulatory modules of cohesin functions and get insights into the molecular bases of cohesin-related diseases. These ambitious goals will be achieved using multi-disciplinary hypothesis-driven and exploratory approaches while promoting a culture of communication and cooperation among academic and private institutions across the European Union. A team of ten PhD students will be trained by the CohesiNet consortium to address these scientific questions and be empowered with skills that will enhance their career perspectives, while experiencing first-hand the value of Open Science and the importance of inclusion, transparency, accessibility and integrity in scientific research.

Original text from CORDIS.

Participants

  • CONSIGLIO NAZIONALE DELLE RICERCHE · RomaCoordinatorItaly
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisFrance
  • FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH · WienAustria
  • FUNDACAO CALOUSTE GULBENKIAN · LisboaPortugal
  • FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III · MadridSpain
  • GENOMIC VISION SA · BagneuxFrance
  • IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS · MilanoItaly
  • INNOVATION ACTA SRL · SIENAItaly
  • LUMICKS BV · AmsterdamNetherlands
  • PLASTICELL LIMITED · LondonUnited Kingdom
  • STICHTING AMSTERDAM UMC · AmsterdamNetherlands
  • STICHTING VU · AmsterdamNetherlands
  • THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEUnited Kingdom
  • UNITED KINGDOM RESEARCH AND INNOVATION · SWINDONUnited Kingdom
  • UNIVERSIDAD AUTONOMA DE MADRID · MadridSpain
  • UNIVERSIDADE CATOLICA PORTUGUESA · LISBOAPortugal
  • UNIVERSIDADE NOVA DE LISBOA · LisboaPortugal
  • UNIVERSITA DEGLI STUDI DELLA CAMPANIA LUIGI VANVITELLI · CasertaItaly
  • UNIVERSITAET DUISBURG-ESSEN · EssenGermany
  • UNIVERSITAT WIEN · WienAustria
  • UNIVERSITE DE TOULOUSE · ToulouseFrance
  • UNIVERSITY OF GALWAY · GalwayIreland

Links

Data: CORDIS, © European Union