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Research Programmes

Cell & Developmental Biology

Gene translation laboratory

lribas

Lluis Ribas de Pouplana

Principal Investigator
ICREA Research Professor

Office Tel : +34 93 403 48 68
Lab Tel : +34 93 403 48 67
e-mail : lluis.ribasirbbarcelona.org

Background

Our research addresses the evolution of protein synthesis machinery, the molecular interactions that regulate it, and the biomedical applications that can be derived from its study in human pathogens.

Our initial efforts have focused on the characterization of tRNA recognition mechanisms in two major groups of human pathogens (Plasmodium and Trypanosoma). Additional projects examine the protein synthesis apparatus in mitochondria, the modular evolution of aminoacyl-tRNA synthetases, and the mechanisms for the maintenance of genetic code fidelity in human cells.

Research Interests

Our general objective is to convert our academic understanding of tRNA biology into biomedical applications. This approach is justified by the large body of experimental data that has accumulated on tRNA aminoacylation, and by the essential role of this reaction in biology. In parallel, using tRNA and aminoacyl-tRNA synthetases as tools, we aim to better understand the evolution of life in general, and of the eukaryotic cell in particular.

Research Lines

a. Developing new methods of antibiotic selection.

The development of new antibiotics, including methicillin, the quinolones, and vancomycin, among many others, has always resulted on the appearance of antibiotic-resistant strains of pathogenic bacteria. Thus, there is an increasing need for novel antibiotics, and for the development of more efficient methods for their discovery.

Aminoacyl-tRNA synthetases (ARS) are the enzymes that translate the genetic code by aminoacylating tRNAs. ARS are ideal targets for antibiotic development because they are essential enzymes of universal distribution, whose ancestral nature allows for the selection of specific inhibitors that act solely upon synthetases of pathogenic organisms. This project seeks to generate a new strategy for the rapid and efficient identification of specific ARS inhibitors from large chemical libraries.

b. Genome evolution in human protozoan parasites.

In Entamoeba histolytica we have discovered that the only KRS gene present contains an additional domain that is not found in any other species (Castro and Ribas de Pouplana, unpublished). Genomic sequencing and comparisons with closely related species has allowed us to conclude that the addition of this domain is a relatively recent event. This situation allows us to study a significant genome-shuffling episode soon after its occurrence. By comparing homologous enzymes before and after this domain addition we seek to elucidate the evolutionary pathways of this enzyme, and try to determine the function of this new addition to its structure.

c. Mitochondrial aminoacylation and disease model in Drosophila.

Our goal is to reconstruct human disease caused by aminoacylation deficiencies in mitochondria. We are currently characterizing the aminoacylation activity of the enzyme seryl-tRNA synthetase of Drosophila melanogaster. This organism uses two forms of this enzyme, and we hypothesize that one of these is directed and functional in the mitochondria. We aim to characterize this protein and, through its mutation, to generate a Drosophila model of mitochondrial disease. The misacylation or poor activity of mitochondrial tRNAser in humans is responsible for a variety of muscular diseases. However, this phenotype is due to mutations in the mitochondrial genome, which are extremely difficult to reproduce and study. By mutating the enzyme (whose gene is coded in the nuclear genome), we aim to generate an equivalent phenotype that is more amenable to analysis.

d. The importance of aminoacylation editing in human cells.

We study the mechanism of misacylation correction in human cells, and, in particular, the capacity of these cells to correct errors in tRNA charging induced by mischarging enzymes from other organisms. We have cloned the enzyme isoleucyl-tRNA synthetase from Streptococcus pneumoniae, and we have used valine to knock out its capacity to correct the misacylation of tRNAIle. The resulting enzyme generates this erroneous product with high frequency, thereby causing generalized protein mutations. We are currently examining the mechanisms of human cell response to this insult.

Funding

This group receives financial support from the  following sources:

  • Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
  • Generalitat de Catalunya (Government of Catalonia)
  • European Union
  • ICREA (Institució Catalana de Recerca i Estudis Avançats)(Catalan Institute of Research and Advanced Studies)
More info

Scientific publications search

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Research Directory

Core facilities and Services Directory

  • Generalitat de catalunya
  • Generalitat de catalunya. Salut
  • Universidad de Barcelona
  • Parc cientific

Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10-12
08028 Barcelona - Spain
Tel: (+34)93 403 7111 | Fax: +34 93 403 7114
infoarrobairbbarcelona.org