Research & Core Facilities

Bioinformatics and Genomics

Coordinator: Roderic Guigó

The research groups in the Bioinformatics and Genomics Programme have as an overarching goal the understanding of the encoding of biological information in the sequence of the genomes (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 level. Our research also includes developing basic alignment methodologies tailored to functional genomic domains exhibiting specific patterns of sequence conservation, and investigating how the evolution of these domains is correlated with the evolution of the encoded phenotypic traits. We are also interested in uncovering the very basic molecular events that govern evolutionary processes. Finally, the programme aims to translate the understanding of the human genome sequence into knowledge about diseases. The year 2013 was crucial for this programme, which was redesigned to include the former Genes and Disease programme.


Cell and Developmental Biology

Coordinator: Vivek Malhotra

The major focus of our programme is understanding the mechanism of cell compartmentation, cell division, and tissue organisation. The specific interests of the group leaders include protein sorting and secretion (Malhotra), microtubule dynamics and chromosome segregation (Vernos, Mendoza), cytoskeleton dependent RNA transport (Maurer), cell migration and their assembly into a tissue (Solon and Malhotra), and lipid and protein homeostasis (Carvalho). The approaches being used to address these issues include genome-wide screens, live cell and whole animal imaging, cell-free assays, as well as biophysical and mathematical modelling. Our studies take advantage of several model systems including yeast, frogs, flies and mammalian tissue cell cultures. The department has biweekly data clubs and a yearly retreat to discuss new developments. We have a number of collaborative projects and we encourage more joint efforts in the development of technology, procedures and the training of young scientists to address challenging issues of fundamental importance. Some of our key findings in the year 2013 include the identification of genes required for mucin secretion in human cancer cells, regulation of sterol homeostasis by the ubiquitin ligase Doa10/Teb4, and the role of Aurora A mediated NEDD1 phosphorylation in chromosomal microtubule nucleation and spindle function. Malhotra, Mendoza and Carvalho are funded by grants from the ERC. Malhotra received the MERCK award from the American society of biochemistry and molecular biology (ASBMB) and Carvalho is a recipient of the international early career scientist award from HHMI and was elected an EMBO Young Investigator.


Gene Regulation, Stem Cells and Cancer

Coordinator: Juan Valcárcel

This year our programme saw the departure of Salvador Aznar-Benitah’s group. After six highly productive years at the CRG he took a senior position at the Institute for Research in Biomedicine (IRB) in Barcelona. During its time at CRG, his group made very important contributions to the field of adult stem cells, particularly regarding the influence of circadian rhythms in skin stem cell homeostasis. While we will greatly miss Salva and his group, we are very glad that the hugely successful research programme he built up at the CRG made him an international leader in his field and provided his group with excellent opportunities and a great scientific environment in which to continue his work on the other side of the city.

The year was rich in important scientific findings on a wide variety of topics, from establishing the roles of RNAs in chromatin remodelling to identifying the diverse roles of Polycomb complexes in stem pluripotency. From discovering the function of mRNA transport in the control of sex determination in flies to finding ways to trigger neural reprogramming with very promising potential for retina regeneration.

Remarkable findings by the group of Bill Keyes, in collaboration with the group of James Sharpe (Systems Biology Programme), documented the fact that cell senescence, a process previously known to play a role in ageing and in defence against tumours, also occurs during normal development and can actually instruct embryonic patterning. Another scientific highlight of the year was the discovery by the groups of Thomas Graf and Miguel Beato that a brief pulse of C/EBPα, a transcription factor previously known to induce the transdifferentiation of B cells into macrophages, can covert B cells into induced Pluripotent Stem (iPS) cells at high efficiencies when subsequently exposed to a cocktail of four transcription factors (known as the Yamanaka factors) that promote the expression of gene pluripotency. This finding may have important basic and clinical implications for understanding the generation and applications of iPS cells.

Finally, an achievement of special value for the CRG was the award of an ERC Synergy grant to the groups of Miguel Beato, Guillaume Filion, Thomas Graf and Marc Martí-Renom, to support their collaborative efforts to understand the three-dimensional organisation of the genome, its dynamics and functional consequences.


Systems Biology

Acting coordinator: James Sharpe

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 wide range 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 goals the programme is strongly interdisciplinary, comprising an increasing number of physicists, mathematicians and computer scientists, in addition to biologists. This year saw the addition of a new group to the programme, Mara Dierssen’s lab on Cellular and Systems Neuroscience, and the departure of Mark Isalan’s group, whose successful 7 years at the CRG has resulted in a move to Imperial College London.

In 2013, group leaders from our programme were honoured with a number of prestigious prizes, including the Eppendorf Young Investigator Award presented to Ben Lehner, and the President’s Medal from the Society for Experimental Biology awarded to Johannes Jaeger. The programme also received many new international grants, including Swarm-Organ a European project coordinated by James Sharpe, and the ERC Proof of Concept project MycroBiotics coordinated by Luis Serrano. As in previous years, we organised a very successful one-week summer school on modelling in systems biology, with an international team of lecturers and attracting students from around the world. This year we also organised the CRG Symposium on Biological Control Networks uniting different systems from bacteria to vertebrate development under the unifying theme of network analysis.


CORE FACILITIES

Director: Mònica Morales

The core facilities and the technologies they offer continue to be a valued cornerstone of the research performed at the CRG. The programme currently comprises six Core Facility Units: Genomics, Proteomics, Advanced Light Microscopy, Biomolecular Screening & Protein Technologies, FACS, and Bioinformatics, as well as the Histology Service and the Storage and Computing Unit that are only accessible to internal users. As in previous years, the overall activity in core facilities continued to increase.

The Scientific IT Unit, in charge of the storage and computing cluster at the CRG, became part of the Core Facilities Programme in June 2013. In July, Carlo Carolis was appointed Manager of the Biomolecular Screening & Protein Technologies Unit. In September, Doris Meder left the CRG and Mònica Morales took up her position as the new Head of Core Facilities.

The major equipment upgrades in 2013 have been: 1) An Illumina HiSeq 2500 in the Genomics Unit; and 2) An ABSciexTriple-TOF 5600 mass spectrometer in the Proteomics Unit.

In order to improve the services provided to the users, each Core Facility Unit is working on individual technology development and implementation projects as time and capacity allows. In 2013, the major technologies implemented were: Flow Karyotyping in the FACS Unit, the monitoring of phospho-peptides by data-independent acquisition in the Proteomics Unit, Microscale Thermophoresis in the BMS&PT Unit, automated library preparation in the Genomics Unit, currently set up for RNA sequencing applications, and the Galaxy portal in the Bioinformatics Unit. The ALMU Unit has, since October 2013, been hosting the beta-test of a Leica next-generation STED system (STED3X), incorporating unique features (e.g., axial STED) and displaying major improvements in image quality.

The CRG core facilities are not only well established locally, with users coming from different institutions in Barcelona and Spain (as well as from abroad), but they are also recognised partners in European initiatives. The Advanced Light Microscopy Unit is a partner in the ESFRI initiative EuroBioimaging, the Genomics Unit is a transnational access site in the European infrastructure network ESGI, and the Proteomics Unit is a transnational access and research site within the European Infrastructure network PRIME-XS as well as being the only Spanish Proteomics Facility listed in the European MERIL platform.

The Core Facilities are member of the Core Facilities Excellence Alliance “Core For Life” (www.core4life.eu), which also includes the EMBL, VIB (Belgium), MPI-CBG (Dresden, Germany), IMP and CSF (Vienna, Austria), as well as the Functional Genomics Centre Zurich. The aim of Core For Life is to share and consolidate procedures, join efforts in personnel training and technology validation, share access to facilities across institutes, and lobby for infrastructure funding at EU level.