Molecular Oncology Programme

Chromosome Dynamics Group

Group Leader:  Ana Losada
Overview

Our research focuses on a protein complex named cohesin that is essential for chromosome organisation. Cohesin mediates sister chromatid cohesion and, thereby, ensures faithful DNA repair by homologous recombination and proper chromosome segregation during cell division. It also plays a major role in the spatial organisation of the genome by promoting long-range DNA looping, which in turn contributes to transcriptional regulation, organisation of DNA replication factories and locus rearrangement by recombination. Mutations in cohesin have recently been found in several tumour types, most prominently in bladder cancer and acute myeloid leukaemia. Mutations in cohesin and its regulatory factors are also at the origin of a group of human syndromes collectively known as cohesinopathies.

Our goal is to understand how cohesin works, how it is regulated and how its dysfunction contributes to cancer and other human diseases. In particular, we are intrigued by the existence of different versions of the cohesin complex in somatic cells. We use mouse models carrying knock out alleles of genes encoding cohesin subunits to investigate their functional specificity, both at the cellular level and in the context of an organism. We also take advantage of the Xenopus egg cell-fee system to explore additional aspects of cohesin regulation.