This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement Nº 847635.
Department of Microbiology and Parasitology
Faculty of Pharmacy
The research group which develops research and teaching activities at the Department of Microbiology and Parasitology (UCM), is also part of the Ramón y Cajal Institute for Health Research (IRYCIS). The group, currently composed of 9 researchers including 5 PhDs, 3 predoctoral reasearchers and two technicians and led by Prof. Javier Arroyo (ResearchID: E-9308-2016) has been funded continuously since 1998 through more than forty research projects granted by national (CICYT, FIS), regional (CAM) and European Union agencies. The scientific goals of the group focus on the characterization of biological mechanisms relevant for fungal cell wall biogenesis and morphogenesis, the characterization of transcriptional and post-transcriptional mechanisms and MAPK signalling pathways that regulate gene expression in response to cell wall stress, most of them in the context of genomic strategies, as well as in their application towards the search for new antifungals. The group has published more than 100 research articles on these topics in many indexed journals, 70% of them in Q1 and more than 30% D1, including: Nature, Nature Reviews Microbiology, Nature Communications, EMBO J, Mol Cell Biology, Nucleic Acids Research, Trends Microbiol, J Cell Science, Molecular Microbiology, Cellular Microbiology, J Biol Chem, etc, participating also in numerous agreements with biotech and pharmaceutical companies engaged in the discovery of novel drug candidates (MSD, Spain; Fundación Medina, Spain).
Facilities include all those required for yeast molecular biology, cellular biology and functional genomics approaches: microscopes, thermalcyclers, orbital incubators, ultracentrifuges, refrigerated centrifuges, Nanodrop 200c, Speed-Vac, Fast-Prep, Microplate fluorescent readers, DNA and protein electrophoresis systems; Fluorescence Imaging System Odyssey; flow cytometer, etc, located at the Department and others accesible through UCM Research Support Centers: DNA MiSeq (Illumina); 3730 DNA Analyzer, Real Time PCR System, Bioanalyzer and Affymetrix GeneChips (Genomics Unit); Proteomics Analyzer with TOF/TOF, segmented linear ion trap LTQ, Q-TOFII and capillary liquid chromatography coupled to collector in MALDI plate (Proteomics Unit); Cell sorter cytometer and confocal and multiphoton microscopes (Flow cytometry and Fluorescence Microscopy Unit). Material resources include collections of yeast mutants in non-essential and essential genes, as welll as ORF-GST overexpression.
The fungal cell wall has emerged as one of the most attractive targets for therapeutic intervention against fungal infections and the development of new antifungal therapies. However, a very well conserved compensatory adaptive response is elicited by fungi under situations that compromise cell wall integrity diminishing the effectiveness of antifungal therapies using cell wall inhibitors. In consequence, understanding the molecular basis of fungal adaptation through these mechanisms offer the opportunity not only to understand novel basic mechanisms developed by eukaryotic cells to detect and counterbalance different environmental conditions but also to open avenues for designing new antifungal treatment strategies. In this context, some of the most scientific objectives to be covered this field include:
-Characterization of novel molecular mechanisms regulating fungal cell wall integrity (CWI) upon cell wall stress through genome-wide screenings and proteomic approaches.
-Deciphering regulatory and effector mechanisms governing morphogenetic processes associated with stress conditions and their potential connection with cell cycle elements and its regulation through the CWI MAPK pathway.
-Evaluation of stress response effector mechanisms like those associated with cell wall crosslinking and remodeling transglycosylase enzymes, as potential targets for antifungal development, both in vitro and in vivo.
-Characterization of novel transcriptional mechanisms and factors regulating gene expression through the CWI pathway with emphasis on the interaction of these factors with the chromatin and the transcriptional machinery.
-Characterization of novel post-transcriptional mechanisms regulating gene expression through the CWI pathway with emphasis on the role of P-bodies.