Cabecera CBMSO CSIC UAM

Friday, 6th December 2019

Functional organization of the mammalian genome

 

2016 07 26 GrupoMGomez 400px

 


María Gómez

ESciStaff

EPublications

 

Research summary

The packaging of genomic DNA into chromatin profoundly influences nuclear processes such as transcription, replication, repair and recombination. Understanding how chromatin structure modulates the expression and maintenance of the information encoded in eukaryotic genomes, and how these processes take place within the context of a highly complex and compacted genomic chromatin environment is one of the major basic questions in biology.

To tackle this question we employ a variety of genetic systems with impaired chromatin structure and address the replicative, transcriptional, and DNA damage responses to these altered chromatin scenarios with a combination of state-of-the-art approaches from single-molecule to genome-wide analysis. We aim to provide novel and important clues into the mechanisms by which dividing cells respond in an integrated way to chromatin structure defects. This integrative understanding is instrumental for future therapeutical interventions in situations of nucleosome loss, such as cellular aging and some developmental diseases.

Our lab belongs to the “Network of excellence” CHROMOdyst (MINECO).

We welcome commited applicants to do their Master thesis, PhD, or postdoc in our group. If you are interested in joining us, please send an updated cv and a motivation letter to María Gómez (This email address is being protected from spambots. You need JavaScript enabled to view it.).

 

Latest publications

Almeida, R., Fernández-Justel, J. M., Santa-María, C., Cadoret, J. C., Cano-Aroca, L., Lombraña, R., Herranz, G., Agresti, A. and Gómez, M. 2018. Chromatin conformation regulates the coordination between DNA replication and transcription. Nat Commun, 9:1590.

Lombraña, R., Álvarez, A., Fernández-Justel, J. M., Almeida, R., Poza-Carrión, C., Gomes, F., Calzada, A., Requena, J. M. and Gómez, M. 2016. Transcriptionally driven DNA replication programme of the human parasite Leishmania major. Cell Rep, 16: 1-13.

Lombraña, R., Almeida, R., Revuelta, I., Madeira, S., Herranz, G., Saiz, N., Bastolla, U. and Gómez, M. 2013. High-resolution analysis of DNA synthesis start sites and nucleosome architecture at efficient mammalian replication origins. EMBO J. 32: 2631-2644.

 

MGomez Picture

Structure and Function of Macromolecular Complexes

 

Santiago RamonB 400px

 


Santiago Ramón-Maiques

 

ESciStaff

EPublications

 

 

Research summary:

Safeguarding genome integrity is essential for correct cell functioning and to prevent diseases such as cancer. Our group is interested in having a good understanding of central cellular processes affecting the integrity of the genome such as the metabolism of nucleotides, the replication, recombination and repair of DNA, and the maintenance and recognition of chromatin architecture. These tasks are performed by proteins and other macromolecular components that associate forming complex and fascinating cellular machines. We combine protein engineering, X-ray crystallography, single-particle electron microscopy, together with biochemical and functional studies, to understand the structure and function of these macromolecular complexes at the atomic level. This knowledge should guide us in the design of compounds to modulate the activity of these machines, providing new opportunities and strategies for fighting disease.

 

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We study the structure and function of CAD, a multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidine nucleotides. This protein is composed of four enzymatic domains: glutaminase (GLN), carbamoyl phosphate synthetase type II (CPS-II), dihydroorotase (DHO) and aspartate transcarbamoylase (ATC).

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Structures of the DHO and ATC domains of human CAD determined by X-ray crystallography.

       

 

Relevant publications:

  • Moreno-Morcillo M, Grande-García A, Ruiz-Ramos A, Del Caño-Ochoa F, Boskovic J, Ramón-Maiques S. Structural Insight into the Core of CAD, the Multifunctional Protein Leading De Novo Pyrimidine Biosynthesis. Structure. 2017 Jun 6;25(6):912-923.e5. doi: 10.1016/j.str.2017.04.012. Epub 2017 May 25. PubMed PMID: 28552578.
  • Ruiz-Ramos A, Velázquez-Campoy A, Grande-García A, Moreno-Morcillo M, Ramón-Maiques S. Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA. Structure. 2016 Jul 6;24(7):1081-94. doi: 10.1016/j.str.2016.05.001. Epub 2016 Jun 2. PubMed PMID: 27265852.
  • Dramićanin M, López-Méndez B, Boskovic J, Campos-Olivas R, Ramón-Maiques S. The N-terminal domain of MuB protein has striking structural similarity to DNA-binding domains and mediates MuB filament-filament interactions. J Struct Biol. 2015 Aug;191(2):100-11. doi:10.1016/j.jsb.2015.07.004. Epub 2015 Jul 10. PubMed PMID: 26169224.
  • Grande-García A, Lallous N, Díaz-Tejada C, Ramón-Maiques S. Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD. Structure. 2014 Feb 4;22(2):185-98. doi: 10.1016/j.str.2013.10.016. Epub 2013 Dec 12. PubMed PMID: 24332717.
  • Mizuno N, Dramićanin M, Mizuuchi M, Adam J, Wang Y, Han YW, Yang W, Steven AC, Mizuuchi K, Ramón-Maiques S. MuB is an AAA+ ATPase that forms helical filaments to control target selection for DNA transposition. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2441-50. doi: 10.1073/pnas.1309499110. Epub 2013 Jun 17. PubMed PMID: 23776210; PubMed Central PMCID: PMC3703974.

 

Genome Dynamics and Function

      Functional organization of the mammalian genome

 

 

2016 07 26 GrupoMGomez 400px

 


María Gómez

ESciStaff

EPublications

 

Research summary:

One of the most fascinating challenges in genome biology is deciphering the non-coding genomic landscape, as the majority of the eukaryotic complexity is encoded in our regulatory elements. Studies in our lab focus on the functional relationship between the regions that regulate DNA replication initiation and transcription initiation, and how these nuclear processes take place within the context of a highly complex and compacted genomic chromatin environment.

During the last years, we studied how nucleosomes and chromatin structure influence the activation of DNA replication initiation sites using two complementary experimental systems: (i) mammalian genetic systems with altered DNA-nucleosome ratios, and (ii) the particular genomic arrangement of the early branched eukaryote Leishmania major. Collectively, we found that chromatin configurations strongly impact on the replication initiation landscape and that both the spatial and the temporal programme of DNA replication are linked to RNA polymerase kinetics. Building-up from that work, we are currently exploring in detail how replicating cells respond to altered chromatin scenarios and, in particular, how the crosstalk between transcription and replication is established to ensure genome stability. This integrative knowledge is of fundamental importance as there is mounting evidence showing that impairment in the coordination between both processes is a strong source of genomic instability, and that cellular aging and certain developmental disorders are associated with impaired chromatin structure and global genomic instability. To this aim we use a variety of genetic systems with altered chromatin structure, and address the replicative, transcriptional, and DNA damage responses to these chromatin scenarios with a combination of state-of-the-art approaches from single-molecule to genome-wide analysis.


 

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Latest publications:

  • Lombraña, R., Álvarez, A., Fernández-Justel, J. M., Almeida, R., Poza-Carrión, C., Gomes, F., Calzada, A., Requena, J. M. and Gómez, M. 2016. Transcriptionally driven DNA replication programme of the human parasite Leishmania major. Cell Rep, 16: 1-13.
  • Lombraña, R., Almeida, R., Revuelta, I., Madeira, S., Herranz, G., Saiz, N., Bastolla, U. and Gómez, M. 2013. High-resolution analysis of DNA synthesis start sites and nucleosome architecture at efficient mammalian replication origins. EMBO J. 32: 2631-2644.
  • Sequeira-Mendes, J., Diaz-Uriarte, R., Apedaile, A., Huntley, D., Brockdorff, N. and Gómez, M. 2009. Transcription initiation activity sets replication origin efficiency in mammalian cells. PLoS Genet. 5: e1000446.
  • Gómez, M. and Antequera, F. 2008. Overeplication of short DNA regions during S phase in human cells. GenesDev. 22: 375-38.

 

Regulation of gene expression in Leishmania

 FotoGrupo 26Jul17

 


José María Requena Rolanía 

ESciStaff

EPublications

Research summary:

 

The research activity of our group has been focused on molecular aspects of the protist Leishmania and the immunopathology that the infection of this parasite causes. On the one hand, we have continued studying molecular processes associated with the peculiar mechanisms of gene expression in an organism in which transcriptional regulation is almost absent. On the other hand, we have conducted activities aimed to develop strategies to control leishmaniasis, a disease that continues affecting millions of people worldwide.

 

By using massive sequencing techniques, we are studying the transcriptomes of several Leishmania species (and improving the genomic annotations) with the goal of identifying both regulatory cis-elements, often found in the 3’ untranslated regions (UTRs) of mRNAs, and RNA-binding proteins (RBPs), as key players in the regulation of gene expression. These tasks are being done in close collaboration with Dr. Begoña Aguado (also at CBMSO). In order to give visibility to the results of our studies and to facilitate the use of the generated data, we have designed the Web page Leish-ESP (http://leish-esp.cbm.uam.es/).

 

Within the research line on immunopathological aspects of leishmaniasis, headed by Dr. Manuel Soto, we are studying the interactions between Leishmania and the mammalian immune system, characterizing parasite factors able to interfere with the induction of protective immune responses. Additionally, new strategies for the development of specific treatments, diagnostic systems as well as vaccines are being explored from the analysis of samples derived from human and canine patients, together with animal models of experimental leishmaniasis. Also, we are participating in a project granted by the European Commission’s FP7 Cooperation Work Program for Health; this project entitled Clinical Studies on a Multivalent Vaccine for Human Visceral Leishmaniasis (MuLeVaClin; EU contract 603181) is aimed to develop a vaccine against human visceral leishmaniasis (http://www.mulevaclin.eu). Finally, as members of the Tropical Diseases network (ISCIII; http://www.ricet.es/es/), our group is engaged in collaborative activities with clinical teams.

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 Regulation of gene expression in Leishmania occurs exclusively at the post-transcriptional level

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 

Publications:

  • Requena, J.M., Chicharro, C., Garcia, L., Parrado, R., Puerta, C.J. and Cañavate, C. (2012). Sequence analysis of the 3'-untranslated region of HSP70 (type I) genes in the genus Leishmania: its usefulness as a molecular marker for species identification. Parasites & Vectors 5: 87. PMID: 22541251
  • Rastrojo, A., Carrasco-Ramiro, F., Martín, D., Crespillo, A., Reguera, R.M., Aguado, B. and Requena, J.M. (2013). The transcriptome of Leishmania major in the axenic promastigote stage: transcript annotation and relative expression levels by RNA-seq. BMC Genomics 14(1):223. PMID: 23557257
  • Fraga, J., Montalvo, A.M., Van der Auwera, G., Maes, I., Dujardin, J.C., and Requena, J.M. (2013). Evolution and species discrimination according to the Leishmania heat-shock protein 20 gene. Infect Genet Evol 18: 229-237. PMID: 23722022
  • Ramirez, C.A., Requena, J.M., and Puerta, C.J. (2013). Alpha tubulin genes from Leishmania braziliensis: genomic organization, gene structure and insights on their expression. BMC Genomics 14, 454. PMID: 23829570
  • Ramirez, C.A., Dea-Ayuela, M.A., Gutierrez-Blazquez, M.D., Bolas-Fernandez, F., Requena, J.M., and Puerta, C.J. (2013). Identification of proteins interacting with HSP70 mRNAs in Leishmania braziliensis. J. Proteomics 94: 124-137. PMID: 24060997
  • Montalvo, A.M., Fraga, J., Rodriguez, O., Blanco, O., Llanos-Cuentas, A., Garcia, A.L., Valencia, B.M., Muskus, C., Van der Auwera, G., and Requena, J.M. (2014). Detección de Leishmania spp. en base al gen que codifica la proteína HSP20. Rev Peru Med Exp Salud Publica 31: 635-643. PMID: 25597712
  • Nocua, P.A., Ramirez, C.A., Barreto, G.E., Gonzalez, J., Requena, J.M., and Puerta, C.J. (2014). Leishmania braziliensis replication protein A subunit 1: molecular modelling, protein expression and analysis of its affinity for both DNA and RNA. Parasites & Vectors 7: 573. PMID: 25498946
  • Requena, J.M., Montalvo, A.M., and Fraga, J. (2015). Molecular Chaperones of Leishmania: Central Players in Many Stress-Related and -Unrelated Physiological Processes. Biomed Res Int 2015: 301326. PMID: 26167482
  • Alonso, G., Rastrojo, A., Lopez-Perez, S., Requena, J.M., and Aguado, B. (2016). Resequencing and assembly of seven complex loci to improve the Leishmania major (Friedlin strain) reference genome. Parasites & Vectors 9: 74. PMID: 26857920
  • Fernandez-Orgiler, A., Martinez-Jimenez, M.I., Alonso, A., Alcolea, P.J., Requena, J.M., Thomas, M.C., Blanco, L., and Larraga, V. (2016). A putative Leishmania DNA polymerase theta protects the parasite against oxidative damage. Nucleic Acids Res 44: 4855-4870. PMID: 27131366
  • Lombraña, R., Alvarez, A., Fernandez-Justel, J.M., Almeida, R., Poza-Carrion, C., Gomes, F., Calzada, A., Requena, J.M., and Gomez, M. (2016). Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major. Cell Rep 16: 1774-1786. PMID: 27477279
  • Requena, J.M., Rastrojo, A., Garde, E., Lopez, M.C., Thomas, M.C., and Aguado, B. (2017). Genomic cartography and proposal of nomenclature for the repeated, interspersed elements of the Leishmania major SIDER2 family and identification of SIDER2-containing transcripts. Mol Biochem Parasitol 212, 9-15. PMID: 28034676
  • Requena, J.M., Rastrojo, A., Garde, E., Lopez, M.C., Thomas, M.C., and Aguado, B. (2017). Dataset for distribution of SIDER2 elements in the Leishmania major genome and transcriptome. Data Brief 11, 39-43. PMID: 28127581
  • Solana, J.C., Ramirez, L., Corvo, L., de Oliveira, C.I., Barral-Netto, M., Requena, J.M., Iborra, S., and Soto, M. (2017). Vaccination with a Leishmania infantum HSP70-II null mutant confers long-term protective immunity against Leishmania major infection in two mice models. PLoS neglected tropical diseases 11, e0005644. PMID: 28558043
  • Nocua, P.A., Ramirez, C.A., Requena*, J.M., and Puerta*, C.J. (2017). Leishmania braziliensis SCD6 and RBP42 proteins, two factors with RNA binding capacity. Parasites & vectors 10, 610. *C.A. PMID: 29258569
  • Gonzalez-de la Fuente, S., Peiro-Pastor, R., Rastrojo, A., Moreno, J., Carrasco-Ramiro, F., Requena*, J.M., and Aguado*, B. (2017). Resequencing of the Leishmania infantum (strain JPCM5) genome and de novo assembly into 36 contigs. Sci Rep 7, 18050. *C.A. PMID: 29273719
  • Diaz, J.R., Ramirez, C.A., Nocua, P.A., Guzman, F., Requena, J.M., and Puerta, C.J. (2018). Dipeptidyl peptidase 3, a novel protease from Leishmania braziliensis. PLoS One 13, e0190618. PMID: 29304092

 

Books:

Stress Response in Microbiology. Caister Academic Press. Editor: Jose M. Requena. June 2012. ISBN: 978-1-908230-04-1. NLM ID: 101587947


 

Patents:

Jose M. Requena Rolanía, J.M., Cristina Folgueira Fernández, C., Carrión Herrero, J. y Manuel Fresno Escudero, M. (2010) Use of strains of Leishmania ΔHSP70-II as a vaccine. Universidad Autónoma de Madrid. PCT/ES2010/070073.

Chromosome replication and genome stability


 Jose Antonio Tercero Grupo400

 


José Antonio Tercero

ESciStaff

EPublications

Research summary:

The maintenance of genome integrity during chromosome replication and the fidelity of DNA synthesis are essential for the correct transmission of genetic information in every cell division cycle. Inevitably, chromosome replication is threatened by DNA damage, which is a potential source of errors and a risk for the stability and progression of replication forks. Successful genome duplication in every cell cycle requires the repair or tolerance of DNA lesions, the protection of replication forks, and the ability to resume DNA synthesis after fork stalling. Failures in these processes lead to genomic instability, a hallmark of cancer and other diseases, as well as an important causal factor in aging.

Our group is interested in understanding how eukaryotic cells maintain genome stability during chromosome replication, especially under conditions that cause DNA damage or replicative stress. We study how different DNA repair, DNA damage tolerance and checkpoint proteins, in conjunction with some helicases and nucleases, facilitate chromosome replication in the presence of DNA lesions or replication perturbations. We analyse the contribution of these proteins to the integrity and function of replication forks, their regulation and their importance for cell viability under different conditions that cause DNA damage. The main aspects of these processes are evolutionarily conserved, allowing us to use the budding yeast Saccharomyces cerevisiae as a working model organism. 


 

Recent Publications:

  • Gallo-Fernández M, Saugar I, Ortiz MA, Vázquez MV, Tercero, JA (2012) “Cell cycle-dependent regulation of the nuclease activity of Mus81-Eme1/Mms4”. Nucleic Acids Res. 40: 8325-8335.
  • Saugar I, Vázquez MV, Gallo-Fernández M, Ortiz-Bazán MA, Segurado M, Calzada A, Tercero JA (2013) “Temporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage”. Nucleic Acids Res. 41: 8943-8958.
  • Ortiz-Bazán MA, Gallo-Fernández M, Saugar I, Jiménez-Martín A, Vázquez MV, Tercero JA (2014) “Rad5 plays a major role in the celular response to DNA damage during chromosome replication”. Cell Rep. 9: 460-468.
  • Saugar I, Ortiz-Bazán MA, Tercero JA (2014) “Tolerating DNA damage during eukaryotic chromosome replication” Exp. Cell Res. 329: 170-177.
  • Morafraile EC, Diffley JFX, Tercero JA*, Segurado M* (2015) “Checkpoint-dependent RNR induction promotes fork restart after replicative stress”. Sci. Rep 5: 7886. *Corresponding authors
  • Saugar I, Jiménez-Martín A, Tercero JA (2017) "Subnuclear relocalization of structure-specific endonucleases in response to DNA damage. Cell Rep20: 1553-1562.

 


* If you are interested in joining our group, please write to: This email address is being protected from spambots. You need JavaScript enabled to view it.

Protein synthesis and its regulation in eukaryotes

 

Grupo César de Haro 01 400px

 


César de Haro

ESciStaff

EPublications

Research summary:

In response to different environmental stresses, including viral infection, nutrient deprivation, and ultraviolet light exposure, the transient phosphorylation of the a subunit of translation initiation factor 2 (eIF2α) rapidly reduces global protein synthesis, which lowers energy expenditure and facilitates reprogramming of gene expression to remediate stress damage. Our recent work has been focused on these major lines:

1) Regulation of cell cycle and sexual differentiation by eIF2α kinases in Schizosaccharomyces pombe. There is a differential response of the three members of this kinase family to nutrient deprivation-mediated stress, being phosphorylation of eIF2α essential for the proper G1-phase cell cycle arrest and for the cell mating in the absence of nitrogen, leading to their survival.

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 In S. pombe eIF2α phosphorylation is required for proper G1 phase cell cycle arrest when growing in the absence of nitrogen. (A) Using flow cytometry, it is observed that in the absence of nitrogen eIF2αS52A cells, which express a non-phosphorylatable eIF2α, significantly retard arrest in G1 phase of the cell cycle. (B) The optical (Nomarski) and fluorescent (DAPI) micrographs show that, unlike the wild-type cells (WT) which move from G2-M to G1 by division and rounding, eIF2αS52A cells continue to elongate without producing cell division.

2) Ccr4-Not complex is a coordinator of different aspects of gene expression regulation, from mRNA synthesis to degradation. We have studied the relationship of several Ccr4-Not complex proteins with stress response in Schizosaccharomyces pombe. Through protein-protein interaction and genetic relationship we have unravel the mechanistic links between stress-activated MAPKs and Ccr4-Not complex.

Recently, our group and Dr Iván Ventoso group have joined together in order to better develop our objectives: i) to study the mechanisms by which cells detect and respond to distinct stress forms (ultraviolet radiation, nutrient deprivation) through the activity of eIF2α kinases; ii) exhaustive description of the translational reprogramming in response to stress, by using mouse and fission yeast S. pombe as models; iii) identification of mRNA sequences and structures, together with protein factors, involved in the above mentioned reprogramming of gene expression; iv) to study the implications of these processes in longevity and in the development of age-related diseases (cancer).

Figure 2         Scheme of translation reprogramming during stress response in mouse and fission yeast.

 

Recent publications:

Rodríguez-Gabriel, M.A. (2014) Analyzing Cdc2/Cdk1 activation during stress response in Schizosaccharomyces pombe. Methods Mol. Biol. 1170, 383-392.

Jiménez-Díaz, A., Remacha, M., Ballesta, J.P.G. and Berlanga, J.J. (2013) Phosphorylation of initiation factor eIF2 in response to stress conditions is mediated by acidic ribosomal P1/P2 proteins in Saccharomyces cerevisiae. PLoS One 8, e84219.

García-Santamarina, S., Boronat, S., Calvo, I.A., Rodríguez-Gabriel, M.A., Ayté, J., Molina, H. and Hidalgo, E. (2013) Is oxidized thioredoxin a major trigger for cysteine oxidation? Clues from a redox proteomics approach. Antioxid Redox Signal. 18, 1549-1556.

Fernández-Vázquez, J., Vargas-Pérez, I., Sansó, M., Buhne, K., Carmona, M., Hermand, D., Rodríguez-Gabriel, M.A., Ayté, J., Leidel, S. and Hidalgo, E. (2013) modification of tRNA(Lys) UUU by elongator is essential for efficient translation of stress mRNAs. PLoS Genet. 9, e1003647.

Matia-González, A.M., Hasan, A., Moe, G.H., Mata, J. and Rodríguez-Gabriel, M.A. (2013) Functional characterization of Upf1 targets in Schizosaccharomyces pombe. RNA Biol. 10, 1057-1065.

Martín, R., Berlanga, J.J. and de Haro, C. (2013) New roles of the fission yeast eIF2alpha kinases Hri1 and GCN2 in response to nutritional stress. J. Cell Sci.. 126, 3010-3020

Del Pino, J., Jiménez, J.L., Ventoso, I., Castelló, A., Muñoz-Fernández, M.A., de Haro, C. and Berlanga, J.J. (2012) GCN2 has inhibitory effect on human immunodeficiency virus-1 protein synthesis and is cleaved upon viral infection. PLoS One. 7, e47272.

 


 

Recent Doctoral theses:

Marina Portantier (2013). Papel del complejo Ccr4-Not en la respuesta a estrés mediada por la MAPK Spc1 en Schizosaccharomyces pombe. Universidad Autónoma de Madrid. Supervisor: Miguel Ángel Rodríguez Gabriel.

Javier del Pino García (2012). Interacción funcional de la eIF2alfa quinasa GCN2 con el virus de la inmunodeficiencia humana VIH-1. Universidad Autónoma de Madrid. Supervisors: Juan José Berlanga & César de Haro.

Ruth Martín Martín (2012). Caracterización funcional de las eIF2alfa quinasas de Schizosaccharomyces pombe en distintas situaciones de estrés. Universidad Autónoma de Madrid. Supervisors: César de Haro & Juan José Berlanga.

 

Genome Dynamics and Function

          Viral proteins that modify gene expression

 

 

 Grupo-400

 


 

 

Luis Carrasco

ESciStaff

EPublications

 

 

 

 

Research summary:

Our research group is studying different viral proteins that are harmful for mammalian cells during viral replication. We are also analysing the mechanisms that regulate translation of cellular and viral mRNAs. We have focused our attention on two groups of cytopathogenic viral proteins: proteases and viroporins. In addition, we have devoted part of our research efforts to elucidate the presence of fungal infections as potential cause of several human diseases of unknown ethiology. Viral proteins. Recently, we have revised the different existing viroporins and their mode of action. These proteins are encoded by a variety of viruses and exhibit adverse effects on several cellular functions. The main activity of viroporins during the virus life cycle is to promote the exit of new virus particles from infected cells (Figure 1).

Our group has dedicated particular attention to the study of picornavirus and HIV proteases. We have examined the effect of these proteases on translation of several mRNAs and the correlation with the hydrolysis of different translation factors. Notably, we have found that picornavirus proteases 2A and L are able to confer independence for eIF2 during the translation of viral mRNAs.

Regulation of translation. We have described that some viral mRNAs are translated by a dual mechanism and require different initiation factors according to the context of their translation. Sindbis virus constitutes a good model system for these studies. Translation of the subgenomic mRNA from this virus does not utilize several initiation factors. Recently, we have described the eIF4A independence for the translation of this subgenomic mRNA in the infected cells, but this factor is necessary for translation in cell free systems. At present, we are carrying out different constructs that modify the structure of this subgenomic mRNA to determine with more precision its mechanism of translation.


 

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Viroporins promote the budding of new virus particles from cellular membranes.

 

   

Publications:

    • Sánchez-Martínez, S., Madan, V., Carrasco, L. and Nieva, J.L. Membrane-active peptides derived from picornavirus 2B viroporin. Current Protein Pept. Sci. 13, 632-643 (2012).
    • Pisa, D., Alonso, R. and Carrasco, L. (2011) Fungal infection in a patient with multiple sclerosis. J. Clin. Microbiol. Infect. Dis.30, 1173-1180.
    • Castelló, A., Alvarez, E. and Carrasco, L. (2011) The multifaceted poliovirus 2A protease. Regulation of gene expression by picornavirus proteases. J. Biomed. Biotechnol. 2011:369648.
    • Welnowska, E., Sanz, M.A., Redondo, N. and Carrasco, L. (2011) Translation of viral mRNA without active eIF2: the case of picornaviruses. PLos One, 6(7), e22230
    • Alvarez, E., Castelló, A., Carrasco, L. and Izquierdo, J.M. (2011) Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease. Biochem. Biophys. Res. Commun. 414, 142-147.

 

Doctoral theses:

Natalia Redondo Sevillano (2012). Requerimiento de factores de iniciación para la traducción de mRNAs de picornavirus. Universidad Autónoma de Madrid. Luís Carrasco y Vanesa Madan y Miguel Ángel Sanz.

Ewelina Welnowska (2012).Independencia de factores de iniciación en la traducción de los mRNAs virales. Universidad Autónoma de Madrid. Luís Carrasco/Alfredo Castelló.

Genome maintenance and variability: enzymology of DNA replication and repair


Grupo-400

 


Luis Blanco

ESciStaff

EPublications

Research summary:

Since the last 13 years, our group is focused in the study of two eukaryotic DNA polymerases involved in DNA double-strand break repair (DSBs) in humans: Polλ and Polμ, discovered in Blanco laboratory. Due to their role in the Non-Homologous-End-Joining (NHEJ) pathway of DSB repair, these two enzymes are crucial to maintain genome stability, but also to generate the required variability to specific genes, i.e. antigen receptors. Site-directed mutants and chimaeric versions of these two DNA polymerases are being analyzed to unravel the structural basis of their different specificity and catalytic efficiency. In vivo analysis of Polλ and Polμ function is being carried out by using cellular and mouse models of deficiency in one or both of these enzymes, particularly on their impact in genomic stability, aging and neurological disorders. In collaboration with Aidan Doherty (GSDC, Univ Sussex, UK) we have also characterized the polymerase involved in the NHEJ pathway of some bacteria as Mycobacterium tuberculosis, whose mechanism is convergent with that of Polλ y Polμ.

 Fig01-300

Model of the interaction of Polµ with the Ku heterodimer and the DNA substrate, through the BRCT domain.

 

Our lab has recently characterized a novel primase/polymerase, PrimPol, in human cells, able to tolerate lesions in DNA as those produced by oxidative damage and ultraviolet irradiation. As recently shown in collaboration with Ian Holt (MRC, UK), PrimPol has a role in mitochondrial DNA maintenance, and perhaps its deficiency could be at the heart of some human mitochondriopathies. In collaboration with Juan Méndez (CNIO, Spain) we showed that PrimPol also has a role in nuclear DNA replication, specifically in re-priming stalled replication forks that arise in response to replicative stress. Moreover, we have obtained a mouse model of PrimPol deficiency (KO) which is viable, and that will be characterized paying special attention at mitochondrial-dependent phenotypes, and at its value as a model for aging and tumorogenesis.

 

 

 


 

----  Fig ingles-300

 

A novel human DNA polymerase able to tolerate DNA lesions. PrimPol, is located at both DNA compartments: nucleus and mitochondria. The inset at the right shows alternative functions of PrimPol during DNA replication. When a replicative polymerase is blocked at a DNA lesion, PrimPol can act as a “classical” TLS polymerase, "reading" lesions as 8oxoG. If the lesion is "unreadable", PrimPol can reinitiate DNA synthesis ahead of the lesion, by means of its DNA primase activity. PrimPol would be recruited at the single stranded region generated by continued helix opening after the replicative DNA polymerase got stalled at a lesion. Such a “TLS primase” activity would allow replication fork progression, but a lesion-containing gap would be left behind for later repair.

 

 

Publications:

  • Brissett NC, Pitcher RS, Juarez R, Picher AJ, Green AJ, Dafforn TR, Fox GC, Blanco L* and Doherty AJ* (*corresponding author) (2007) Structure of a NHEJ polymerase-mediated DNA synaptic complex. Science 318, 456-459. PMID:17947582.
  • Andrade P, Martin MJ, Juarez R, Lopez de Saro F and Blanco L (2009) Limited terminal transferase in human DNA polymerase mu defines the required balance between accuracy and efficiency in NHEJ. PNAS106, 16203-16208. PMID:19805281.
  • Brissett NC, Martin MJ, Bartlett EJ, Bianchi J, Blanco L, Doherty AJ (2013) Molecular Basis for DNA Double-Strand Break Annealing and Primer Extension by an NHEJ DNA Polymerase.Cell Reports 5(4):1108-20.
  • García-Góméz S, Reyes A, Martínez-Jiménez MI, Chocrón ES, Mourón S, Terrados G, Powell C, Salido E, Méndez J, Holt IJ, and Blanco L (2013) PrimPol, an archaic primase-polymerase operating in human cells. Mol Cell 52(4):541-53.
  • Mourón S, Rodriguez-Acebes S, Martínez-Jiménez MI, García-Gómez S, Chocrón S, Blanco L, Méndez J. (2013) Repriming of DNA synthesis at stalled replication forks by human PrimPol. Nat Struct Mol Biol. 20(12):1383-9.

 

Other activities:

- Organization of the Cantoblanco Workshop: "Polymerases involved in DNA replication, repair and mutagenesis". Organized by Margarita Salas, Luis Blanco, Robert P. Fuchs and Miguel García-Díaz. Universidad Autónoma de Madrid. June 5-7, 2012.
- Coordinator of the module (BM6): "Estabilidad de la Información Genética: Replicación, Reparación y Mutagénesis", Master of Molecular and Celular Biology, Universidad Autónoma de Madrid (UAM).


 

Doctoral theses:

Maria José Martín Pereira (2011). Exclusive polymerases repairing DNA breaks, the same magics from bacteria to man. Universidad Autónoma de Madrid. Luis Blanco Dávila.

Sara García Gómez (2013). PrimPol, una nueva primasa/polimerasa en células humanas. Universidad Autónoma de Madrid. Luis Blanco Dávila.

Ana Gómez Bedoya (2013). Análisis estructura-función de la DNA polimerasa lambda humana y su implicación en la reparación del DNA mediante NHEJ. Universidad Autónoma de Madrid. Luis Blanco Dávila.

Ana Aza Montoya (2014). In vivo role of DNA polymerases lambda and mu in Genome Stability. Universidad Autónoma de Madrid. Luis Blanco Dávila.


 

Patents:

Inventors: Luis Blanco, Angel Picher. Title: "Method for Genotyping". Patent number: P056358WO S001. Priority country: España. Priority date: PCT sent on February 2012. Owner: X-Pol Biotech S.L.

Virología y microbiología

         African swine fever virus

 

 

 grupo-400

 


María L. Salas Falgueras

BSciStaff

BPublications

 

Research summary:

The African swine fever virus (ASFV) protease that processes the viral polyproteins is required for a late maturational step in virus core assembly and production of infectious progeny virus. On the other hand, studies on ASFV morphogenesis have shown a correlation between proteolytic processing of polyproteins and correct virus assembly, suggesting that the activity of the protease might be modulated during the infection. Indeed, recent studies demonstrated that the protease activity is controlled by two disulfide bridges formed between cysteines C14 and C24 and between C45 and C50. To investigate the mechanism of this redox regulation, we have studied the interaction of the wild type protease and punctual mutants of the involved cysteines to serine with the substrate polyprotein pp62. Our results show, in pull down experiments, the binding of the wild type but not the mutated protease to polyprotein pp62, indicating that the intramolecular disulfide bonds are necessary for the interaction of the protease with its substrate.

          nnnnn     Fig1 300px
  Cells infected with the recombinant virus inducible in the PK. A. Viral factory. B. Viral particles at the plasmatic membrane for exit from the cell..

The function of ASFV genes in virus replication is being studied by the generation of virus recombinants where de gene under study is placed under the control of an IPTG inducible promoter. We have constructed a virus recombinant inducible in gene R298L coding for a viral protein kinase (PK), showing that the PK is not expressed under repression conditions in the absence of IPTG. Under these conditions, infectious intracellular and extracellular virus is produced and the viral particles are morphologically indistinguishable from those produced in an infection with the parental virus. These results indicate that the viral PK is dispensable for the replication of the virus in cells in culture.


 

Selected Publications:

  • Salas, M. L. and Andrés, G. (2013) African swine fever virus morphogenesis, Virus Res.173, 29-41.
  • Rodríguez, J. M. and Salas, M. L. (2013) African swine fever virus transcription. Virus Res. 173, 15-28.
  • Redrejo-Rodríguez, M., Rodríguez, J. M., Suárez, C., Salas, J. and Salas, M. L. (2013) Involvement of the reparative DNA polymerase pol X of African swine fever virus in the maintenance of viral genome stability. J. Virol. 87, 9780-9787.
  • Redrejo-Rodríguez, M. and Salas, M. L. (2014) Repair of base damage and genome maintenance in the Nucleo-Cytoplasmic Large DNA Viruses. Virus Res. 179, 12-25.
  • Lacasta, A., Ballester, M., Moteagudo, P. L., Rodríguez, J. M., Salas, M. L., Accensi, F., Pina-Pedrero, S., Bensaid, A., Argilaguet, J., López-Soria, S., Hutet, E., Lepotier, M. F. and Rodríguez, F. (2014) Expression library immunization can confer protection against lethal challenge with African swine fever virus. J. Virol. 88, 13322-13332.

Internal initiation of translation in eukaryotic mRNAs

 

Grupo400

 


Encarnación Martínez-Salas

ESciStaff

EPublications

 

 

Research summary:

Our main interests are focused to understand the principles guiding alternative mechanisms of translation initiation in eukaryotes. This includes structural and functional analysis of non-coding regions, and identification and characterization of RNA-binding proteins (RBPs) interacting with internal ribosome entry sites (IRES). Genomic and proteomic approaches lead us to identify the network of interactions of RBPs that perform key roles on gene expression. A representative example is Gemin5, the RNA-binding protein of the SMN complex. Defects on the SMN complex cause SMA (Spinal muscular atrophy), an autosomal rare disease. This multifunctional protein performs a critical role in translation control (Fig. 1). Gemin5 harbors a bipartite non-conventional RNA-binding site (RBS1-RBS2) on its C-terminal region, while the N-terminal domain contains 14 WD repeats that mediate the interaction with the ribosome. Using a CLIP-based procedure to search for the cellular targets of the RBS1 domain we identified an internal region of Gemin5 mRNA as a hit of RBS1. Functional analysis of this hit unveiled a feedback loop with its own mRNA, counteracting the negative effect of Gemin5 on translation.

We continue our efforts to understand RNA regulatory elements with the aim to explain the coding potential of eukaryotic genomes, expanding the number of RNAs that can be translated using cap-independent mechanisms under normal conditions or cellular stress. IRESs substitute the function of the 5’ terminal cap present in conventional mRNAs, which is the anchoring point of the translation machinery. To achieve their function, distinct IRESs assemble ribonucleoprotein complexes, which include a subset of eIFs and diverse RBPs. In all cases, RNA structure and IRES function is tightly coupled. Our specific aims were the identification of of factors modulating IRES activity, the evaluation of synergism and/or interference with other factors involved in translation control, and the understanding of RNA structural constraints which are essential for its activity. Fig. 2 shows the conformational changes observed by SHAPE upon incubation of the IRES with native ribosomes. Our findings could allow the prediction of IRES-like motifs in the cellular transcriptome, as well as to infer the role of novel RBPs harboring non-conventional RBDs in translation control.

 

figure 1

Fig. 1

 

figure 1

Fig. 2

 


 

Relevant publications:

  • Francisco-Velilla R, Embarc-Buh A, Martinez-Salas E (2019) RNA-binding modes impacting on translation control: the versatile multidomain protein Gemin5. BioEssays 41(4):e1800241.
  • Fernandez-Chamorro J, Francisco Velilla R, Ramajo J, Martinez-Salas E (2019) IRES-driven RNA localization at ER-Golgi compartment is mediated by RAB1b and ARF5. Life Sci Alliance 2(1). pii: e201800131.
  • Lozano G, Francisco-Velilla R, Martinez-Salas E (2018) Deconstructing IRES elements: an update of structural motifs and functional divergences. Open Biology 8 (11).  pii: 180155.
  • Rodriguez-Pulido M, Sanchez-Aparicio MT, Martinez-Salas E, Garcia-Sastre A, Sobrino F, Saiz M (2018) Innate immune sensor LGP2 is cleaved by the leader protease of foot-and-mouth disease virus. Plos Pathog 14(6): e1007135.
  • Francisco-Velilla R, Fernandez-Chamorro J, Dotu I, Martinez-Salas E (2018) The RNA landscape of the non-canonical RNA-binding domain of Gemin5 unveils a feedback loop with its own mRNA counteracting the negative effect on translation. Nucleic Acids Res 46, 7339-7353.
  • Lozano G, Francisco-Velilla R, Martinez-Salas E (2018) Ribosome-dependent conformational flexibility changes and RNA dynamics of IRES domains revealed by differential SHAPE. Sci Rep 8(1): 5545.
  • Martínez-Salas E, Francisco-Velilla R, Fernandez-Chamorro J, Embarek MA (2018) Insights into structural and mechanistic features of viral IRES elements. Front Microbiol 8:2629.
  • Galan A, Lozano G, Piñeiro D, Martinez-Salas E (2017) G3BP1 interacts directly with the FMDV IRES and negatively regulates translation. FEBS J 284, 3202-3217.
  • Diaz-Toledano R, Lozano G, Martínez-Salas E (2017) In-cell SHAPE uncovers dynamic interactions between the untranslated regions of the foot-and-mouth disease virus RNA. Nucleic Acids Res 45, 1416-1432.
  • Francisco-Velilla, R., Fernandez-Chamorro, J., Ramajo, J., and Martínez-Salas, E. (2016) The RNA-binding protein Gemin5 binds directly to the ribosome and regulates global translation. Nucleic Acids Res 44, 8335-8351.
  • Lozano, G, Jimenez-Aparicio R, Herrero S, Martínez-Salas E (2016) Fingerprinting the junctions of RNA secondary structure by an open-paddle wheel diruthenium compound. RNA 22, 330-338.
  • Lozano G, Fernandez N, Martínez-Salas, E (2016) Modeling three-dimensional structural motifs of viral IRES. J Mol Biol 2016, 428, 767-776.
  • Fernandez-Chamorro J, Lozano G, Garcia-Martin JA, Ramajo J, Dotu I, Clote P, Martínez-Salas E (2016) Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements. Sci Rep 6, 24243.
  • Garcia-Martin JA, Dotu I, Fernandez-Chamorro J, Lozano G, Ramajo J, Martínez-Salas E, Clote P (2016) RNAiFold2T: constraint programming design of thermo-IRES switches. Bioinformatics 32, i360-i368.
  • Lozano G, Trapote A, Ramajo J, Elduque X, Grandas A, Robles J, Pedroso E, Martínez-Salas E. (2015) RNA local flexibility perturbation of the IRES element induced by a novel ligand inhibits viral RNA translation. RNA Biol 12, 555-568.
  • Lozano G, Martínez-Salas E. (2015) Structural insights into viral IRES-dependent translation mechanisms. Curr Opin Virol 12, 113-120.
  • Piñeiro D, Fernandez-Chamorro J, Francisco-Velilla R, Martínez-Salas E (2015) Gemin5: a multitasking RNA-binding protein involved in translation control. Biomolecules 5, 528-544.
  • Martínez-Salas E, Francisco-Velilla R, Fernandez-Chamorro J, Lozano G, Diaz-Toledano R (2015) Picornavirus IRES elements: RNA structure and host protein interactions. Virus Res 206, 62-73.
  • Francisco-Velilla R, Fernandez-Chamorro J, Lozano G, Diaz-Toledano R, Martínez-Salas E (2015) RNA-protein interaction methods to study viral IRES elements. Methods 91, 3-12.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Martinez-Salas+E

eplication of Bacteriophage ø29 DNA

 

Grupo

 


Margarita Salas

 

ESciStaff

 

EPublications

 

 

 

Research summary:

We have continued with the study of ø29 DNA replication initiated by TP-priming. We have dissected the role of the TP DNA binding residues in the replication of the viral DNA. Also, we have determined that the aromatic residue Phe230 is one of the determinants that allows the positioning of the penultimate nucleotide at the polymerization active site to direct insertion of the initiator dAMP. We have identified one site in the TP that allows the insertion of peptides up to 17 amino acids while maintaining the ability to support DNA amplification in vitro. In relation to the ø29 DNA polymerase, in collaboration with Dr. Borja Ibarra, we have determined the mechanism of translocation during processive DNA replication. Besides, we have carried out a global transcriptional analysis of virus-host interactions between ø29 and Bacillus subtilis, finding genes that are up-regulated and others that are down-regulated. On the other hand, we have purified and characterized the DNA polymerase of phage Bam35, that infects Bacillus thuringiensis, with the finding that it is a very faithful polymerase that can couple strand displacement to processive DNA synthesis. In addition, it is able to perform abasic sites translesion synthesis. We have also characterized the Bam35 TP and shown that it is used as primer in the initiation of replication of the viral DNA. In collaboration with Dr. Nadine Fornelos, we have shown that protein gp7 of the B. thuringiensis phage GIL01, regulates transcription interacting with the bacterial LexA repressor.

We have generated a recombinant of African swine fever virus (ASFV), BA71 isolate, that is deleted in the viral gene CD2v, homologous to the celular CD2. This recombinant, designated BA71∆CD2, is highly attenuated in vivo and has demonstrated to confer very solid protection against experimental challenge with lethal homologous and heterologous ASF viruses.

 

figure 1

Fig. 1: Bacteriophage Bam35 as a new working model for protein-primed DNA replication: early steps of TP-DNA replication. A novel single-nucleotide jumping back is involved in Bam35 genome replication (middle row), in comparison with ø29 sliding back and adenovirus jumping back.

 


 

Publications:

  • Mojardín, L., Botet, J., Moreno, S. and Salas, M. (2015). Chromosome segregation and organization are targets of 5´-Fluorouracil in eukaryotic cells. Cell Cycle 14, 206-218.
  • Holguera, I., Muñoz-Espín, D. and Salas, M. (2015). Dissecting the role of DNA-binding residues of the ø29 terminal protein in viral DNA replication. Nucleic Acids Res. 43, 2790-801.
  • Morin, A,. Cao, F.J., Lázaro, J. M., Arias-Gonzalez, J.R., Valpuesta, J. M., Carrascosa, J.L., Salas, M. and Ibarra, B. (2015). Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase. Nucleic Acids Res. 43, 3643-3652.
  • Köhler, K., Duchardt-Fener, E., Lechner, M., Damm, K., Hoch, P.G., Salas, M. and Hartmann, R.K. (2015). Structural and mechanistic characterization of 6S RNA from the hyperthermophilic bacterium Aquifex aeolicus. Biochimie 117, 72-86.
  • Berjón-Otero, M., Villar, L., de Vega, M., Salas, M. and Redrejo-Rodríguez, M. (2015). DNA polymerase from temperate phage Bam35 is endowed with processive polymerization and abasic sites translesion synthesis capacity. Proc.Natl.Acad.Sci.USA. 112, 3476-3484.
  • Fornelos, N., Butala, M., Hodnik, V., Anderluh, G., Bamford, J. K. and Salas, M. (2015). Bacteriophage GIL01 gp7 interacts with host LexA repressor to enhance DNA binding and inhibit RecA-mediated auto-cleavage. Nucleic Acids Res. 43, 7315-7319.
  • del Prado, A., Lázaro, J.M., Longás, E., Villar, L., de Vega M. and Salas, M. (2015). Insights into the determination of the templating nucleotide at the initiation of 29 DNA replication. J.Biol.Chem. 290, 27138-27145.
  • Salas, M., Holguera, I., Redrejo-Rodríguez, M. and de Vega, M. (2016). DNA-binding proteins essential for protein-primed bacteriophage ø29 DNA replication. Frontiers in Molecular Biosciences. 3, 37.
  • Berjón-Otero, M., Villar, L., Salas, M. and Redrejo-Rodríguez, M. (2016). Disclosing early steps of protein-primed genome replication of the Grampositive tectivirus Bam35. Nucleic Acids Res. 44, 9733-9744.
  • Mojardín L. and Salas, M. (2016). Global transcriptional analysis of virus-host interactions between phage ø29 and Bacillus subtilis. J. Virol. 90, 9293-9304.
  • Gella, P., Salas, M. and Mencía, M. (2016). Engineering permissive insertion sites in the bacteriophage Phi29 DNA-linked terminal protein. PLoS One, 11, 164901.
  • Salas, M. (2016). My scientific life. Bacteriophage 6, 1271250.
  • Suarez, C., Andrés, G., Kolovou, A., Hoppe, S., Salas, M. L., Walther, P. and Krijnse Locker, J. (2015). African swine fever virus assembles a single membrane derived from rupture of the endoplasmic reticulum. Cellular Microbiol. 17, 1683-1698.
  • Lacasta, A., Monteagudo, P. L., Jiménez-Marín, A., Accensi, F., Ballester, M., Argilaguet, J., Galindo, I., Segalés, J., Salas, M. L., Domínguez, J., Moreno, A., Garrido J. J. and Rodríguez, F. (2015) Live attenuated African swine fever viruses as ideal tools to dissect the mechanisms involved in viral pathogenesis and immune protection. Veterinary Research 46,135 DOI: 10.1186/s13567-015-0275-z.
  • Rodríguez, J. M., Moreno, L. T., Alejo, A., Lacasta, A., Rodríguez, F. and Salas, M. L. (2015) Genome sequence of African swine fever virus BA71, the virulent parental strain of the nonpathogenic and tissue-culture adapted BA71V. PLoS One Nov.30; 10 (11): e0142889. Doi: 10.1371/journal.pone.0142889. eCollection.
  • Hernaez, B., Guerra, M., Salas, M. L. and Andrés, G. (2016) The uncoating of African swine fever virus: a stepwise disassembly process that culminates in inner envelope fusion at multivesicular endosomes. PLoS Pathog 12 (4): e105595 doi:101371/journal.ppat 1005595.

 


 

Chapter book:

  • Salas, M. and de Vega, M. (2016). Protein-primed replication of bacteriophage ø29 DNA. In: Laurie S. Kaguni and Marcos Túlio Oliveira, editors, The Enzymes, Vol. 39, Burlington: Academic Press, pp 137-167.
  • de Vega, M., Lázaro, J.M. and Salas, M. (2016). Improvement of ø29 DNA polymerase amplification performance by fusión of DNA binding motifs. New Enzymes Useful in Rolling Circle Amplification (RCA). Springer, Demidov Ed. 10.1007/978-3-319-42226-8, pp 11-24.404.

 


 

Scientific Activities:

  • Co-dirigió la asignatura de Estabilidad de Genomas: Replicación, Reparación y Mutagénesis del Master Biología Molecular y Celular englobado en el Programa Oficial de Posgrado de Biociencias Moleculares de la Universidad Autónoma de Madrid (2015-2016 y 2016-2017).
  • Co-dirigió el Curso “Biomedicina y Biotecnología en la era genómica” de la Escuela de Biología Molecular “Eladio Viñuela”. Universidad Internacional Menéndez Pelayo (2015). Organizó la XIII y XIV Semana de la Ciencia del Ayuntamiento de Luarca. Asturias 2015 y 2016.
  • Co-dirigió el Curso “La superación de la crisis a través de la Ciencia” de la Escuela de Biología Molecular “Eladio Viñuela”. Universidad Internacional Menéndez Pelayo (2016).

 


 

Awards:

  • Denominación “Margarita Salas” al Bulevar del Parque Tecnológico de Andalucía. Málaga (2015–).
  • Medalla de Honor de la Real Academia Nacional de Medicina (2015).
  • Denominación “Margarita Salas” al IES Sevilla Este. Sevilla (2016–).
  • Medalla Echegaray de la Real Academia de Ciencias Exactas, Físicas y Naturales (2016).
  • Miembro del Consejo Rector de la Agencia Estatal de Investigación (2016–).

 


 

Doctoral Thesis:

  • Alicia del Prado Díaz (2015). Estudios estructurales y funcionales de la DNA polimerasa y la proteína terminal del bacteriófago phi29. Universidad Autónoma de Madrid. Directores: Margarita Salas y Miguel de Vega.
  • Isabel María Holguera López (2015). Estudio del dominio de unión a DNA de la proteína terminal del bacteriófago ø29 y su papel en la replicación del DNA viral. Universidad Autónoma de Madrid. Directores: Margarita Salas y Daniel Muñoz-Espín.
  • Pablo Gella Montero (2016). Optimización del sistema replicativo del bacteriófago phi29 para aplicaciones biotecnológicas. Universidad Autónoma de Madrid. Directores: Margarita Salas y Mario Mencía.

 


 

 ComFuturo-Vertical-Color-POS-Transp.png

 

The CSIC Foundation, through the program ComFuturo, is funding the contract of the researcher Modesto Redrejo Rodríguez for the project "New fusion DNA polymerases with biotechnological applications."

 


 

Currículum Vitae Margarita Salas

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  1. E17.Miguel de Vega - Eng.

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