A look back at the year

Research

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Bioinformatics and Genomics

The overarching goal of the research groups in the Bioinformatics and Genomics Programme is to understand the encoding of biological information in the genome sequence (that is, of the complex relationship between genomes and phenotypes), and how evolutionary forces have contributed to shaping this encoding. The groups are interested in understanding the sequence patterns that instruct the molecular pathway leading from the DNA to protein sequences, and the mechanisms by means of which the outputs of this pathway (RNA and proteins) interact to confer functionality at the molecular and cellular levels. Our research also includes developing basic alignment methodologies tailored to functional genomic domains exhibiting specific sequence conservation patterns, and investigating how the evolution of these domains correlates with the evolution of encoded phenotypic traits. We are also interested in uncovering the very basic molecular events governing evolutionary processes. Finally, the programme aims to translate the understanding of the human genome sequence into knowledge about diseases. In 2013, the programme was redesigned to include the former Genes and Disease programme.

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Cell and Developmental Biology

The scientists in the Cell and Developmental Biology department aim to reveal the mechanisms of cell compartmentation, division and tissue organisation. The department comprises Vivek Malhotra (Mechanism of protein secretion), Isabelle Vernos (Microtubule and spindle dynamics), Manuel Mendoza (Cytokinesis, chromosomal segregation, and cell cycle check points), Pedro Carvalho (Organelle biogenesis and homeostasis), Jerome Solon (Tissue organisation), and Sebastian Maurer (Cytoplasmic RNA localisation). Vivek Malhotra, Manuel Mendoza and Pedro Carvalho are funded by grants from the European Research Council (ERC). Pedro Carvalho is also a recipient of the international early career scientist award from HHMI and in 2013 was elected EMBO Young Investigator. Isabelle Vernos is a member of the Scientific Council of the ERC and also on the Advisory Council for Science, Technology and Innovation of the Spanish Secretariat for Research, Development and Innovation.

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Gene Regulation, Stem Cells and Cancer

A highlight this year was the incorporation of Bernhard Payer as a new group leader in our programme. After very successful PhD and postdoctoral training in the laboratories of Azim Surani (Gurdon Institute) and Jeannie Lee (Harvard University), Bernie is setting up his group to study the process of X chromosome reactivation in embryos, during both induced pluripotent stem cell reprogramming and the formation of the germ cell lineage. His interest in chromatin, epigenetic regulation, X chromosome gene regulation, and cell reprogramming resonates with on-going work in our programme as well as in other programmes at the CRG.

Scientific highlights of groups in the programme during 2014 include several important publications on the mechanisms of cell differentiation and reprogramming, chromatin remodelling and RNA recognition. Collaborative work between the groups of Thomas Graf and Miguel Beato revealed that the transcription factor C/EBP poises B cells for efficient reprogramming into induced pluripotent cells, while work by Pia Cosma’s group demonstrated the importance of temporal fluctuations in signalling pathways for efficient cell reprogramming. Joint research by the groups of Luciano Di Croce and Thomas Graf unveiled a key role for the epigenetic regulator Zrf1 in the differentiation of embryonic stem cells into neural progenitors. Collaboration between the groups of Miguel Beato, Marc Martí-Renom and Guillaume Filion led to the discovery of structural transitions in chromatin topological domains relevant for hormone-induced gene regulation. Finally, work in Fátima Gebauer’s lab revealed how RNA binding by the protein UNR explains functional synergy with Sex-lethal and facilitates interaction between the RNA helicase MLE and the long non-coding RNA roX2, thus regulating two aspects of X chromosome dosage compensation in Drosophila.

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Systems Biology

The research groups in the Systems Biology programme cover a wide range of topics: from dynamic gene regulatory networks to systems neuroscience, and employ a great variety of model systems to address these issues, including prokaryotes, cell lines, C. elegans, Drosophila and mice. Underlying this diversity, however, are the common goals of combining systematic and quantitative data collection, using computational models, going beyond molecular descriptions, and arriving at a deeper dynamic understanding of complex biological processes. To achieve these objectives the programme is strongly interdisciplinary, comprising an increasing number of physicists, mathematicians and computer scientists, in addition to biologists.

2014 was an important year for the programme, as we had our second external evaluation by an international panel (the previous assessment was in 2011). The new head of the CRG’s Scientific Advisory Board, Prof. Veronica van Heyningen (UCL London), chaired the panel, which included 9 eminent researchers from across the world. At the end of the 2-day event, the programme was rated as “excellent at the highest international level”.

In June we welcomed a new group leader to the program, Manuel Irimia. He arrived from the Donnelly Centre in Toronto, and his lab will focus on the roles that alternative splicing and other mechanisms of transcriptomic diversification play in vertebrate embryonic development and evolution. His first success at the CRG was winning one of the prestigious ERC Starting Grants, and two other groups were also awarded large grants: Ben Lehner, won an ERC Consolidator Grant on robustness in development and cancer, and Luis Serrano was granted an H2020 project on engineering Mycoplasma pneumoniae as a broad-spectrum animal vaccine.

Scientifically, 2014 saw a number of exciting discoveries covering a wide variety of topics. At the level of individual molecules and their physical interactions, we generated novel predictions about RASopathies and cancers from structure-energy analysis. In the study of dynamical networks, we reverse-engineered the gap gene system of a non-model species of fly – the moth midge Clogmia albipunctata. At the multicellular level, we demonstrated that a 62-year old theory by Alan Turing explains how fingers and toes are patterned during mouse embryo development, and also showed how the dynamics of gene expression during the development of C.elegans is affected by genetic variation. Finally, at the whole-organism level, we revealed that nicotine addiction may be due to a compensatory strategy in individuals with altered expression of subunits of the nicotinic acetylcholine receptors, and that Drosophila larval chemotaxis employs an error-correction strategy known as weathervaning. More details on these projects can be seen on the individual group pages.