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Projects. Life and Earth Sciences

The structural bases of tumoral development associated with transcription regulating interactome defects

Lead Researcher:
Carlos Fernández Tornero

Research Centre:
Centro de Investigaciones Biológicas (CIB). CSIC. Madrid.

Abstract: 

Carlos Fernández TorneroThe transcription or synthesis of ARN is the first step in gene expression. It is regulated through a dynamic network of interactions between the macromolecules involved in the aforementioned process. Transcriptional alterations have an enormous impact on cellular homeostasis and are directly connected with the development of diseases. Loss of control of cellular proliferation stands out among these, and generally leads to the formation of tumours. An in-depth study of the interactions that regulate this process would therefore make it possible to lay the foundations for the development of new anti-tumoral drugs.

The aim of this project is the structural and functional characterisation of a series of proteins and macromolecular complexes involved in the synthesis of ARN. The project we propose aims to meet this challenge by using an innovative structural approach that combines several experimental techniques to offer a holistic vision of the process. Our approach combines powerful structural methods such as x-ray crystallography and electronic microscopy, genetic studies and classical biochemical studies, together with emerging techniques such as wild-type mass spectroscopy. Our studies will contribute to a better understanding of how ARN synthesis is regulated, as well as developing strategies to study protein complexes and their interactions with other macromolecules.


Researcher's web address:
http://www.chemphysbiol.org/research/fernandez-tornero/ft-lab-home/



Carlos Fernández Tornero

He has dedicated a dozen years to the structural characterisation of the transcription process. He has focussed chiefly on eukaryotic polymerase ARN, the enormous macromolecular complexes that catalyze the aforementioned process. He was the pioneer in the large-scale isolation of these complexes, as well as their characterisation by x-ray crystallography and electron microscopy. His studies, among which the structural determination of polymerase I ARN at atomic resolution stands out, together with the three-dimensional reconstruction of polymerase III ARN as a sub-nonmetric resolution, have given led to enhanced understanding of how these enzymes work. His scientific papers have been published in journals such as Nature, Molecular Cell, Nature Structural Biology and The EMBO Journal. He has also written educational articles for the Huffington Post, the Annals of the Real Academia de Farmacia and the Boletín de la Institución Libre de Enseñanza.


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