ISGlobal

Barcelona Institute for Global Health

The central theme of Luis Izquierdo's laboratory research is the glycobiology of parasites, the functional genomics of carbohydrate-active enzymes and molecular and biochemical parasitology. Parasite surface molecules protect parasites (and other pathogens) and enable them to identify and interact with cells of both the insect vector and the human host. Many of these surface molecules are post-translationally modified by a variety of glycans that modulate binding, recognition and cell protection. We possess extensive knowledge and expertise in the isolation and analysis of parasite surface molecules and metabolites by using advanced liquid chromatography and mass spectrometry methods.

We apply a broad spectrum of approaches, such as bioinformatics, gene-knockout and cell biology, to identify, localise and study the functions of glycoproteins, glycosyltransferases and sugar nucleotide biosynthetic enzymes (1). By generating null, conditional null mutants and knock-downs in parasites and characterizing the biochemical phenotype of the mutant strains created, we have been able to assign functions to glycosylated structures and to the genes involved in glycoconjugate biosynthesis and processing (2). Similarly, by analyzing the metabolites involved in the glycosylation processes (i.e. sugar nucleotides) we have been able to expose new active biosynthetic routes crucial for further glycosylation reactions in the malaria parasite (3).

Our analysis of the sugar nucleotides present in the blood stages of Plasmodium falciparum strongly suggests that these metabolites are involved in the biosynthesis of glycans not yet characterized. Thus, for example, the presence of GDP-fucose in the parasite indicates that this metabolite may be used for further fucosylation reactions. The laboratory is part Barcelona Institute for Global Health Foundation (ISGlobal).

The centre is located in a privileged scientific environment, at the side of the Hospital Clínic de Barcelona (HCB), the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and the Campus of the Facultat de Medicina-Clínic of the Universitat de Barcelona (UB). The main research activity takes place in the Centre Esther Koplowitz (CEK, completed in October 2010; http://bit.ly/1d0GfLF). There exist facilities and support services for FACS analysis, bioinformatics, NMR-Imaging, radiosotopes, electron microscopy (transmission and scanning electron microscopes), optic confocal and standard epifluorescence microscopy, proteomics facility (offering MALDI-Tof, ESI-MS/MS, 2D-SDS electrophoresis and analysis, mass fingerprint and sequence tag services), animal house, genomics and DNA units (offering DNA sequencing and next generation sequencing, capillary electrophoresis for RNA, DNA and protein analysis), etc.

All these facilities and support units are run by highly trained persons who are also able to instruct other research staff in their use and applications and are available for use to the applicant.

Website: http://www.isglobal.org/en

1. Izquierdo L, Güther ML and Ferguson MA. Creation and characterization of glycosyltransferase mutants of Trypanosoma brucei. Methods Mol Biol. 2013;1022:249-275. PMID: 23765667

2. Izquierdo L, Schulz BL, Rodrigues JA, Güther ML, Procter JB, Barton GJ, et al. Distinct donor and acceptor specificities of Trypanosoma brucei oligosaccharyltransferases. EMBO J. 2009 Sep 2;28(17):2650–61. PMID: 19629045

3. Sanz S, Bandini G, Ospina D, Bernabeu M, Marino K, Fernandez-Becerra C, et al. Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum. J Biol Chem. 2013 Jun 7;288(23):16506–17. PMID: 23615908