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Annual Report of Activities CNC 2008 - Center for Neuroscience and ...

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Medical Mycology – Yeast Research | Head: Teresa GonçalvesObjectives1. With the final purpose <strong>of</strong> unravel the resistance<strong>of</strong> C<strong>and</strong>ida albicans to macrophage attack a studywas initiated with the aim to study the role <strong>of</strong>extracellular purines since ATP <strong>and</strong> its metabolite,adenosine, have been implicated in the immuneinflammatoryresponse as STOP signals.2. The increased number <strong>of</strong> yeast infectionsprompted us to study the epidemiology <strong>of</strong> yeastinfections in the Portuguese population attending aCentral Hospital.3. Our recent finding that the yeast Saccharomycescerevisiae responds to bacterial endotoxinactivating the HOG Signalling Pathway [J BiolChem 281: 24687‐24694(2006)] prompted us tostudy the impact <strong>of</strong> such activation in yeastmetabolism.4. With the identification in the dematiaceousfungus Alternaria infectoria <strong>of</strong> AiFKS <strong>and</strong> AiRHO,together with casp<strong>of</strong>ungin susceptibility, took us tostudy the combined effect <strong>of</strong> anti‐fungal cell wallinhibitors in collaboration with Pr<strong>of</strong> Neil Gow <strong>of</strong>the Institute <strong>of</strong> Medical Sciences, University <strong>of</strong>Aberdeeen, UK (manuscripts under preparation).Main Achievements1. Yeast metabolic response to the presence <strong>of</strong>bacterial endotoxin (one paper submitted)2. Combined effect <strong>of</strong> anti‐fungal cell wallinhibitors in A. infectoria: identification <strong>and</strong>cloning <strong>of</strong> the AiFKS gene <strong>and</strong> its regulatorAiRHO; casp<strong>of</strong>ungin susceptibility (2 papers underpreparation)3. Clinical mycology: a pathogenic yeast collectionwith 1000 isolates identified <strong>and</strong> characterisedusing molecular biology; an epidemiological study;a new diagnostic technology is being patented4. An in infection model using macrophage cellsinfected with C<strong>and</strong>ida albicans is currently beingused to study:a. the effect <strong>of</strong> purines <strong>and</strong> purinergic receptors inC. albicans clearance, indicating that adenosinemight affect this process trough specific adenosinereceptors (ongoing work)b. together with the Faculty <strong>of</strong> Medicine <strong>of</strong> Porto astudy was finished indicating that CUG ambiguityin C. albicans affects the phagocytic efficiency (onepaper under preparation)62Fig.1. a. C. albicans cell ingested by RAW264.7 macrophageb.,c. Yeast cells evading macrophage celld. Yeast cells inside the macrophage, <strong>for</strong>ming germ tubee. Yeast cell destroyed by phagolysosome

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