CNC.IBILI

Therapy 5 | Structure

The Medical Microbiology includes 20 members assigned to 2 main lines of research: Medical Mycology/Yeast Research (MMYRG) and Molecular Mycobacteriology. The 2 senior scientists, Teresa Gonçalves and Nuno Empadinhas will keep independent lines of research within the strategic scientific plan defined and will share MMYRG previous facilities to optimize the available resources. The two PIs currently collaborate in 2 FCT funded projects involving a protein crystallography group at IBMC (Porto) and an organic chemistry group at ITQB (Oeiras). One project pursues the consequences of codon ambiguity in C. albicans during infection, joining efforts with FMUP and UA while the other tackles the biosynthesis of rare polysaccharides in nontuberculous mycobacteria and their role in adaptation to the host.

MMYRG includes 4 PhD-holding members, combining expertise in fungal biology and pathogenesis (resistance to antifungals with NAR Gow, U Aberdeen, UK, and influence of the purinergic system and aging with RA Cunha, CNC and JR Meyer-Fernandes, UFRJ, Brasil), molecular microbiology (gut microbiome with JG Jones, CNC, and oral microflora with O Martins, FMUC and Inst Straumann, CH), and fungal immunology (with A. Casadevall, Albert Einstein School of Medicine, USA). The biomedical nature accent of our research results from our membership of FMUC/CHUC; 2 of the PhD students are MDs with translational research projects with CHUC; one is the President of SPP, ESPID. We build collections of specimens and related clinical data, that together with the relationship with hospitals are an added value through asset optimization, allowing us to collaborate with leading teams in fungal virulence and resistance to antifungals, the Aberdeen Fungal Group, UK with N Gow and C Munro and with FMUP, with Pina-Vaz and Gonçalves-Rodrigues or with the biotechcompany – Converde, S.A – and its associate CEV, developers and producers of BLAD a biological fungicide (FMC, USA). We keep mandatory weekly meetings to present data within MMYRG and we regularly invite outside collaborators to discuss data or to launch new project ideas.

The Molecular Mycobacteriology team is composed by 3 Post-doctoral fellows skilled in molecular microbiology, taxonomy, bioinformatics and structure-guided drug discovery with fragment-based approaches (at the Univ. Cambridge with Tom L. Blundell, founder of Astex Pharmaceuticals). A PhD student was trained at the Univ. Guelph (with Anthony J. Clarke) to develop new assays for TB acyltransferases and was also recently involved in the development of an efficient process for synthesis of a crucial TB metabolite (see Objectives) that will be patented. Two Masters students will pursue PhD studies in 2015 with co-supervision of collaborators abroad. A masters student is working in a privately funded project (Inst Piaget) to isolate nontuberculous mycobacteria from hospital settings (CHUC/FCTUC/CNC). All team members meet regularly with the PI to discuss results, milestones and new directions. This PI’s projects, funded by National Science Foundation (FCT), have crystallographers at IBMC (Porto) and organic chemists at ITQB (Oeiras) in the team, and the shared supervision of a PhD student at IBMC. The team was recently awarded with a Mizutani Foundation for Glycoscience grant (Japan). The projects focus on the biosynthetic machinery and physiological relevance of essential polymethylated polysaccharides, attractive targets for new drugs against drug-resistant TB. The ongoing collaborations allowed the determination of the 3D structures of essential enzymes in this pathway (Pereira et al, 2008; Fraga et al, unpublished; Mendes et al, unpublished) and drug design trials started at the U of Cambridge. Enzyme inhibition trials, microbial viability assays, pharmacological profiling and infection models with mutant mycobacteria will be carried out in Coimbra in the scope of the “Molecular and Stem-Cell-based Therapies” strand.