Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre)

The main objective of this Programme is to further insight into cancer related processes by combining computational and structural methods. The strength of the Programme lies in the successful combination of scientific and technical advances facilitated by close collaboration with other CNIO Programmes and cancer related projects.

Our three main research lines can be summarised as follows:

• Understanding the structural basis of cell cycle related complexes, in particular those related to protein kinases.
• Developing and integrating computational methods for the analysis of large scale cancer variation studies.
• Applying structural and computational methods to solve key biological problems in collaboration with experimental groups.

Throughout 2008 the Programme has been comprised of two crystallography groups led by Guillermo Montoya and Jerónimo Bravo respectively, a computational biology group coordinated by Alfonso Valencia, and two units: NMR spectroscopy with Ramón Campos Oliva as Unit Leader, and bioinformatics coordinated by David G. Pisano.

Eva Nogales, Professor of Biochemistry and Molecular Biology, the University of Berkeley, completed her sabbatical visit with us this summer as Visiting Professor, funded by Cátedra de Biomedicina de la Fundación BBVA Award.

Our programme also incorporates an additional Unit which hosts and leads the Central Node of the Spanish National Bioinformatics Institute (INB), a technical platform of the Genoma España, providing the necessary expertise to translate bioinformatics methods into systems that can be used by experimental biologists for the analysis of genomic data.

Jerónimo Bravo announced his departure from the CNIO to accept a new position at the Consejo Superior de Investigaciones Científicas (CSIC) in Valencia where he will continue his work in the crystallography and drug discovery fields. Francesco Gervasio, currently working at the Swiss Federal Institute of Technology Zurich (ETH Zurich), Switzerland, has been recruited to set up and lead a new Computational Biophysics Group.

The Macromolecular Crystallography Group has made notable progress in deciphering the mechanism of action of homing endonucleases. In addition, it has also engineered the in vivo specific recognition DNA binding sites of heterodimeric endonucleases based on the Cre scaffold promoter repair of xeroderma pigmentosum group C mutation. This work was carried out in collaboration with former Group Leader of the CNIO Nuclear Magnetic Resonance Group (until December 2007), Francisco Blanco, Centro de Investigación Cooperativa en Biociencias (CIC-bioGUNE).

The Signal Transduction Group has significantly contributed to the discussion surrounding the modes of action of the SH3 domains of CMS and CIN85 with ligands Cbl or CD2.

Our computational efforts have centered on the analysis of high-throughput cancer genomic results, including genome variation studies and the prediction of the consequences of genetic variation in protein families. This work is developed in the context of the National Human Genome Research Institute (NHGRI, USA) ENCODE scale-up project, and the BioSapiens and ENFIN European Networks of Excellence. One methodology that has produced particularly relevant results for 2008 relates to information extraction in biological text developed around the BIOCREATIVE (Critical Assessment of Information Extraction systems in Biology) challenge.