Periodic Reporting for period 1 - CohesiNet (Cohesin and its regulators: from chromosome dynamics and nuclear architecture to human diseases)
Berichtszeitraum: 2023-01-01 bis 2024-12-31
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/(öffnet in neuem Fenster)).
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/(öffnet in neuem Fenster)).
The main achievements for Period 1 of the action (Timeframe: M1 - M24) are:
1) Creation of cell lines where cohesin subunits or effectors are depleted/mutated (corresponding to Deliverable D18)
2) Generation of a cohesinopathy-mutated cell line panel (including human iPSC lines with cohesinopathy-related mutations ((corresponding to Deliverable D24 and Milestone M5)
1) Creation of cell lines where cohesin subunits or effectors are depleted/mutated (corresponding to Deliverable D18)
2) Generation of a cohesinopathy-mutated cell line panel (including human iPSC lines with cohesinopathy-related mutations ((corresponding to Deliverable D24 and Milestone M5)
The panel of cell lines where cohesin subunits or regulators have been mutated or depleted and the cohesinopathy-mutated human iPSC lines will serve as an invaluable tool for understanding how processes such as cell migration, differentiation, and gene expression patterns are altered in cohesinopathies. This knowledge will provide novel insights into the molecular bases of this devastating diseases for which no cure exists.