Objective Microsporidia like Trachipleistophora hominis and Encephalitozoon cuniculi, are opportunistic parasites of humans with HIV. Around 50% of cases of serious diarrhoea in AIDS patients are associated with microsporidia - 14 different microsporidia have now been isolated. Despite their importance, the genome and cell biology of microsporidia are poorly understood. I will use a multidisciplinary approach incorporating training in bioinformatics, proteomics, cell and molecular biology to investigate the structu re and function of the recently discovered microsporidian mitosome ' the most highly reduced mitochondrion yet discovered. My work will also further basic understanding of the minimal and essential functions of the mitochondrion itself; an organelle that is vital for eukaryotes. My hypothesis is that the mitosome makes iron sulphur (Fe-S) clusters ' a fundamental process for all eukaryotic cells, and whose dysfunction causes inherited mitochondrial diseases like Friedrichs Ataxia. The E. cuniculi genome en codes seven of the proteins involved in this process, but there is no experimental data on their location or function. I will clone and sequence two of the key genes (Nfs1p, Isu1p) from Trachipleistophora hominis, a more tractable experimental system than Encephalitozoon, and produce antibodies to locate their site of activity. I will also perform in vitro tests of enzyme function. I will do this at Newcastle University with Professor Martin Embley, in whose lab the mitosome was discovered, and where there are state-of-the-art facilities for bioinformatics, cell biology, proteomics and light and electron microscopy. I will also use bioinformatics to search the Encephalitozoon genome for the mitosomal import pathway. Preliminary data suggests that the mitosome may have, uniquely, dispensed with one of the main mitochondrial import pathways. Thus this work will improve understanding of yet another fundamental mitochondrial process ' that of protein import. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencescell biologynatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords Fe-S cluster assembly HIV Microsporidia comparative genomics human parasites immunocytochemistry infectious disease mitochondria mitosome proteomics Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.3 - Marie Curie Incoming International Fellowships (IIF) Call for proposal FP6-2002-MOBILITY-7 See other projects for this call Funding Scheme IIF - Marie Curie actions-Incoming International Fellowships Coordinator UNIVERSITY OF NEWCASTLE UPON TYNE Address 6, kensington terrace Newcastle upon tyne United Kingdom See on map Links Website Opens in new window EU contribution € 0,00
