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Structural Biology Programme

Director: Óscar Llorca

In the Structural Biology Programme we aim to understand the structural and molecular details of key processes in cancer, to define the structure of the proteins and complexes involved in these processes and, ultimately, to use all these knowledge for structure-based drug discovery. Collaborations and synergies with other Programmes within CNIO and the combination of different methodologies are essential to achieve these aims and address the complexity of cancer.

Three new groups have recently joined the Structural Biology Program that now counts with three Junior and one Senior Research Groups. The program also has several Core Units: Spectroscopy and NMR, Electron Microscopy (EM), Bioinformatics, Crystallography and Protein Engineering, and Biological Text Mining. These Units provide access, maintenance and expertise to the technologies required for the research performed in the Programme, providing support to the CNIO's research activities. Units are an essential element for the Programme and their activities are also vital to facilitate the access to Structural methods for non-experts.

The Junior groups leaded by Daniel Lietha and Ivan Plaza-Menacho work on structural and mechanistic aspects in cancer cell signalling and protein kinases, with emphasis in the search for new inhibitors in collaboration with the Drug Discovery and Experimental Therapeutic Programme. The Junior group headed by Rafael Fernandez-Leiro and the Senior group leaded by Oscar Llorca work in genome instability and DNA repair pathways.

Frontier Structural Biology in cancer requires a strong component in cryo-EM of macromolecular complexes. The Programme has incorporated the expertise of Rafael Fernandez-Leiro and Oscar Llorca in cryo-EM, which are working together with the EM Unit to set up an upgraded facility for high-resolution cryo-EM. The previous work of Rafael Fernandez-Leiro at the LMB-MRC (Cambridge, UK) will be instrumental to incorporate frontier cryo-EM technologies into CNIO.

The new electron microscope with a direct electron detector, suitable for high-resolution studies of proteins and complexes will bring the cryo-EM revolution to CNIO. Other structural biology technologies already in place in the Programme will be also upgraded in the future to further facilitate the exploitation of the molecular and structural understanding of biological mechanisms for its application in drug design/discovery.