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Scientific Programmes

Structural Biology Programme

Genome Integrity and Structural Biology Group

Group Leader:  Rafael Fernández
Research highlights
DNA Replication & Repair - Focus on mitochondria

Eukaryotic cells have two genomes: nuclear and mitochondrial. However, how the integrity of mitochondrial genome is maintained through the equilibrium between DNA replication, repair and degradation, and organelle dynamics remains still unclear. We are particularly interested in understanding these pathways because of its implications for ageing and disease, and because of its striking differences with its nuclear counterparts. Our group focuses on key questions regarding mitochondrial DNA replication and integrity, and their relation to cancer. Understanding these mechanisms would be extremely valuable, ultimately having an impact on how we understand diseases and how we can develop new ways of tackling them.

cryo-EM

Important recent technological developments in microscopes, detectors and image processing tools have significantly improved the resolution of cryo-EM on what has been termed the "resolution revolution". These advances enable the structural analysis of many elusive proteins and protein complexes to unprecedented level of detail, allowing the study of their molecular mechanisms and the interactions with small molecules. As a result of these advances, cryo-EM has become a mainstream technique for high resolution structural analysis of macromolecules and has emerged as a key new tool for drug-development. We are upgrading our electron microscopy facility and will have access to state of the art microscopes. Combined with many other approaches already stablished at CNIO, we use cryo-EM to study diverse macromolecular complexes involved in cancer with the aim to understand how they work and to move towards the generation of new compounds for therapies.

Collaborators

To study DNA Mismatch Repair pathways and understand the mechanisms behind them and their implication in disease, we collaborate with Titia Sixma at the Netherlands Cancer Research institute and with Meindert Lamers at Leiden University. We continue to work with Sjors Scheres at the LMB-MRC in Cambridge and with Meindert Lamers in Leiden University for developing novel EM applications. We work closely in various projects with Jose María Valpuesta at CSIC-CNB in Madrid, Juan Hermoso at CSIC-Rocasolano in Madrid, and with Oscar Llorca and other groups at CNIO. We are always happy to hear if you are interested in applying cryo-EM in collaborative projects, so get in touch!

Do you want to work with us?

If you want to come and work with us, collaborate with us, or you are just interested in what we do and want to discuss science, please drop us a few lines!

We encourage and support applications to funding agencies and are always looking for talented people to join us. If you like what we are doing and want to get involved, you are welcome to contact us.