.The Cent re for Genomic Regulation (CRG) is an international biomedical research institute of excellence, based in Barcelona, Spain, with more than 400 scientists from 44 countries. The CRG is composed by an interdisciplinary, motivated and creative scientific team which is supported both by a flexible and efficient administration and by high-end and innovative technologies.Alternative splicing (AS) is the important process that allows the production of different messenger RNAs and proteins from a single gene in humans and other complex organisms. AS plays a crucial role in mechanisms controlling gene expression. Mutations affecting AS contribute to the development of many diseases, including cancer and neurodegeneration. While drugs that target AS have recently entered the clinic and provided the first therapy for common genetic disorders, there is still much to be learnt about the mechanisms controlling splicing and their modulation by small molecules. An advance in this field can thus unleash new approaches for the treatment of many diseases of current unmet need. Jointly funded by the European Research Council and UK Research and Innovation, the UNLEASH project aims to use a multidisciplinary, highly collaborative approach to understand how splice site selection is regulated and whether it can be specifically modulated by small molecules. The UNLEASH project will generate many new tool compounds that will help us to study gene function and may also help the development of new therapeutics that target AS. The partners of the UNLEASH project include Profs. Angus Lamond, David Gray (University of Dundee), Michael Sattler (Technical University and Helmholtz Munich) and Juan Valcárcel (CRG, Barcelona). The role of the postdoc to be hired will be to contribute to the characterization of molecular mechanisms of AS regulation, including the identification and analysis of small molecule modulators and their possible applications in medicine.About the teamThe group of Juan Valcárcel at the Center for Genomic Regulation (CRG) of Barcelona has a long trajectory studying pre-mRNA splicing regulation. The group combines high-throughput methods with detailed biochemical and cellular assays and collaborates closely with other groups working on computational and structural biology to study molecular mechanisms and networks of alternative splicing regulation in cancer. The group also develops mechanism-based novel therapeutic approaches for oncology. Juan Valcárcel obtained his PhD from work on influenza virus splicing regulation carried out in the lab of Juan Ortín at the Center of Molecular Biology Severo Ochoa in Madrid. After a postdoc with Michael Green at the University of Massachusetts, working on mechanisms of splice site recognition and regulation, he established his group at the European Molecular Biology Laboratory (EMBL) in Heidelberg in 1996. In 2002 the group moved to the newly created Center for Genomic Regulation (CRG) of Barcelona
