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The aim of this project is to achieve a detailed and precise understanding of how chromatin remodelling complexes work
This research combines three cutting-edge techniques based on the design of non-natural amino acids, cryo-electron microscopy and mass spectrometry
This proposal was one of 21 chosen out of 858 submitted initially to this international programme
The Human Frontiers Science Program will provide 1,050,000 dollars in funding over three years to a project led by Óscar Llorca, director of the Structural Biology Programme at the Spanish National Cancer Research Centre (CNIO), which seeks to provide a more accurate understanding of how chromatin remodelling complexes work. The team coordinated by Llorca is working alongside Mark Skehel’s Laboratory of Molecular Biology (LMB) in Cambridge and Heinz Neumann’s group at the Max Planck Institute in Germany. The project is also grounded in the experience gained by Fabrizio Martino in the study of chromatin. Martino, from the Centre for Biological Research (CIB-CSIC), is also participating in the project.
Some cellular processes are extremely hard to grasp, especially those in which short-lived structures are involved. In such cases, in vitro reconstruction provides limited information, particularly on account of the difficulty reproducing the physiological complexity of the systems.
One clear example is chromatin (the way in which DNA is stored in the cell nucleus) and the hundreds of proteins that regulate and remodel it. These proteins are responsible for “a series of essential modifications to regulate gene expression; a process that is important, for example, in cancer”, explains Llorca. “The problem is that we currently know very little about the protein complexes that make these modifications and how they do it”.

