Trachipleistophora hominis is a member of the microsporidia, a large group of obligate intracellular parasites of other eukaryotes including patients with HIV/AIDS. Microsporidia were originally thought to be early-branching eukaryotes lacking mitochondria. Recent data, key elements published by the proposed host laboratory, have now shown that they are highly reduced fungi with largely metabolically cryptic remnant mitochondria called mitosomes. During their evolution to parasitism the genomes of microsporidians have become highly streamlined, resulting in a strong dependency of the parasites on substrates imported from their hosts. In my project I will analyse the relatively large (~8 Mb) newly sequenced (by the host laboratory) genome of T. hominis and compare it to the much smaller (~3 Mb) published genome of Encephalitozoon cuniculi and to several partial genome sequences from other microsporidians. These analyses will allow me to compare and contrast the degree of reductive genome evolution undergone by different microsporidians during their separate evolutionary histories and adaptation to different hosts. As part of these analyses, I will reconstruct a putative proteome for the T. hominis mitosome, focusing particularly on hypotheses of candidate transport proteins. These hypotheses will then be tested by laboratory work, including localisation studies and functional characterisation. The proposed project, host laboratory and their collaborators will provide me with state of the art training in bioinformatics and molecular biology aimed at understanding the biology of a group of important human parasites. Research on this topic goes to the heart of a fundamental issue for eukaryotic biology - identifying the origin of essential components of eukaryotic cells. It speaks directly to the FP7 Health Priority “Systems Biology” (HEALTH-2007-2.1.2) to combine and integrate data from biological pathways in unicellular eukaryotic organisms to human cells and organs.