This project addresses the problem of how two prokaryotes merged to form the first eukaryotes. Using database searches, sequence alignments, phylogenetic analyses, genome and metabolic resonstructions, we will shed considerable light on the events surrounding eukaryogenesis - the formation of the first euakryotic cells. Eukaryotic cells are discretely different to prokaryotic cells, primarily because of their possession of a true nucleus, decoupled transcription and translation, possession of mitochondria or mitochondrial remnants, Golgi apparatus, mitosis and a host of other features. With the advent of high-throughput technologies, we can begin to build a clearer picture of eukaryogenesis. Recently, our research group has been able to demonstrate that eukaryotic cells consist of a complex community of genes with prokaryotic ancestry and that eukaryote genomes are chimaeric. Genes of Archaebacterial origin tend to be more highly expressed, more likely to be lethal upon deletion in yeast, less likely to be involved in mendelian disease in humans and so forth. We now wish to use new "omics" data in an innovative way to understand who was involved in this merger, to reconstruct the metabolism of first eukaryotes and to understand the first steps in diversification of eukaryotes. The most immediate products of this research will be a collection of publications based on empirical data and relating to eukaryotic origins and early diversification. We will also hold a meeting that will bring together the world's leaders in this field of research and help to piece together the results of several research groups. The enduring impact of this project will be in the way undergraduate textbooks represent our knowledge of eukaryotic origins. At the moment, there is a great deal of uncertainty and we plan on providing important evidence that will mean the students of tomorrow are given a clearer picture of eukaryote origins.