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

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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.