Thursday, 14th December 2017

Overview

The Department of Genome Dynamics and Function (GDF) was created in 2008 and started to function in 2010 by gathering research groups interested in answering questions on fundamental processes of genetic information dynamics, that is, replication, transcription and translation. For this purpose the various groups that integrate the Department cover aspects of the biology of DNA and chromatin, RNA, as well as DNA-, RNA- and protein-protein complexes with the aim of understanding the dynamics of these processes in health and disease. An added value of the groups gathered at GDF is the use of a wide set of model organisms that range from bacteriophages and viruses, to yeast, protozoa or organelles, and multicellular organisms such as plants and mammals.

GDF’s research activities are structured around two major areas: the regulatory mechanisms of genome replication and the expression of the genetic material, including transcription, post-transcriptional regulation and translational control, both in the context of cell proliferation, development and disease. Experimental approaches include molecular, structural, cellular, genetic and genomic approaches.

Groups interested in genome replication control tackle various fundamental aspects of the enzymology of DNA replication with special emphasis on the structural and functional bases of the mechanism of phage ø29 DNA replication initiated by terminal protein (TP) priming (M. Salas) and the study of DNA polymerases Polλ (lambda) and Polμ (mu) involved in DNA double-strand break repair (DSBs), crucial to maintaining genome stability as well as to generating variability of antigen receptors (L. Blanco). Genome stability during chromosome replication, especially under conditions that cause DNA damage or replicative stress, is studied in the model system S. cerevisiae (J. A. Tercero). Two groups focus their efforts on understanding the molecular determinants of DNA replication origin specification and usage in relation to transcriptional activity and epigenetic control using animal and plant model systems (mammalian cells and Arabidopsis thaliana, respectively) (M. Gomez and C. Gutiérrez).

The lab of C. Gutiérrez is also interested in understanding the control of gene expression in relation to cell proliferation and the endocycle transition in Arabidopsis, where it is of primary relevance for cell fate and differentiation decisions as well as for stem cell maintenance. The changes in the transcriptome and the proteome associated with the proliferative phenotype of human cells with reduced expression of TIA1 and TIAR proteins is studied to define their contribution to uncontrolled proliferation (J. M. Izquierdo). The group of L. R. Desviat uses microarrays and massive parallel sequencing to study the molecular basis of inherited metabolic diseases (IMD) and to develop gene specific antisense RNA-based therapy for splicing defects or nonsense mutation suppression. Gene expression control is studied in the protozoan parasite Leishmania, where it occurs largely post-transcriptionally, with the aim of understanding its mechanisms and its implications for serodiagnosis and new immunotherapeutic strategies (J. M. Requena).

Translational regulation of gene expression plays an important role in the onset of cellular response to various stresses. The group of L. Carrasco studies two types of cytopathogenic viral proteins, namely, proteases coded by animal viruses and viroporins. C. de Haro’s group focuses on the cellular response dependent on the transient phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2) through the activation of some of the four eIF2alpha kinases in S. pombe and mammalian cells. A major discovery in the field of gene regulation has been the participation of various structural RNA elements, RNA-binding proteins and noncoding RNAs in translational control. E. Martinez-Salas’s group focuses on the cap-independent translational control of eukaryotic mRNAs by internal ribosome entry sites (IRES), specifically on how ribonucleoprotein complexes drive translation initiation. J. M. Cuezva studies the expression of the rate-limiting protein of energy transduction in mitochondria (β-F1-ATPase) and the mechanisms controlling its translation through mRNA binding proteins and miRNA, and their role in cancer progression. 

The GDF groups maintain various internal collaborations and carry out a number of Departmental activities. These include GDF monthly seminars, where each group presents recent results for discussion, and where we encourage the younger members of each laboratory to participate as well as the PIs. Every year, on average, the GDF invites two scientists for the Severo Ochoa Seminar Series and four scientists for Departmental Seminars organized as part of the yearly CBMSO seminars. In addition, we also host the Madrid Chromatin Club (MCC), coordinated by the three members of the Department (M. Gómez, E. Caro, C. Gutiérrez) and sponsored by Active Motif with the aim of gathering scientists in the Madrid area interested in chromatin and epigenetic mechanisms to exchange ideas and foster collaborations. The main activities of the MCC, launched late in 2011, consist of 4 seminars over the year presented by MCC members or by scientists from abroad.