Sunday, 17th December 2017

fig02Genome Dynamics and Function

             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 (https://leishseq.neocities.org/).

 

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.

fig01.300px

 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

 

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.