Since 2010 ICREA Research Professor at the Molecular Biology Institute of Barcelona (IBMB). (2002) Group Leader at the Center for Genomic Regulation. (1991) Post-doc at the Albert Einstein College of Medicine (New York), working on mechanisms of pre-mRNA splicing in yeast. (1990) PhD in Biochemistry by the Universitat Autònoma de Barcelona (UAB), with research on the regulation of gene expression by the plant hormone absicic acid in maize, supervised by Dr. Montserrat Pagès at the Center for Research and Development (CID), Barcelona. (1988) BA in Sciences (Biochemistry), UAB. IBMB Vice-director Nov 2018 - June 2022.
Most genes bear interruptions by meaningless segments that are to be removed. This task is catalyzed a machine, the spliceosome, akin to a genome’s ghostwriter, possibly the most complex enzyme in an eukaryotic cell. Why such convoluted, dangerous, and wasteful genomic layout, escapes us. But by controlling the spliceosome it is possible to get diverse mRNAs from a single pre-mRNA sequence, enlarging the information content of the genomes. The current model on how the spliceosome works hinges on a “splicing code” that guides the spliceosome and it is built using RNA sequences and RNA-binding proteins. Our goal is to contribute to deciphering this code. For this we follow a reductionist scheme with yeast, using molecular and computational approaches to study the initial steps of splicing and their control. We are finding aspects of the spliceosome that must impact the splicing code itself, implicating that its role in gene expression is even more complex than it is assumed.
Selected research activities
During this period we have been working on three aspects of the spliceosome: 3' splice site recognition when there are multiple choices, how the yeast spliceosome, specialized in messages with one intron, deals with pre-mRNAs with multiple introns (>10), and how introns and exons are being recognized in the absence of regulatory proteins.
To gain experience and knowledge to address these questions using computational tools I have joined Christopher Burge lab at MIT, for a sabbatical period of one year.
In addition to this, I have started a collaboration with the group of Dr. Ignacio Fita, at the IBMB. Fita’s team includes experts on protein structure and protein-protein interactions (Vizarraga (2020) Nature Comm (11): 5188). As our hypothesis is that the spliceosome itself can identify exons, and there is structural data supporting this (Li (2019) Nature (573): 375), I plan on exploring the molecular details of this particular way of substrate recognition, and the experience of Fita’s group on protein interactions will be valuable.