Eukaryotic organelles, parasites and multicellularity: comparative genomic and proteomic approaches.

Understanding how complex single-celled organisms evolved into the super-kingdoms of Life over the last 2 billion years is a fundamental question in biology. We propose to use advanced genomic sequencing, microscopy, computation, cell biology and proteomics to reveal the mechanisms behind some major evolutionary transitions of biomedical significance: We will address how many groups of single-celled organisms have independently adapted to life without oxygen. These include forms that are free-living in the environment, and many that parasitize humans or other animals, especially parasites of the gut. We will explore how these species have modified their cell compartments and genomes to acquire new biochemical pathways suited to low-oxygen habitats, such as the human gut, and investigate other ways in which the genomes of single-celled parasites have changed to allow them to live within their hosts. We will also examine how single celled organisms first evolved into primitive animals. We will target a protein complex that is involved in holding groups of animal cells together, but is also present in some single-celled microbes, where it must have a different role. This will allow us to better understand the functions of proteins important to our own multicellular bodies and develop new model systems in which to study them. There are several of potential practical benefits of the proposed research. The species examined include close relatives of serious human pathogens; revealing unique aspects of their biology could help identify new drug targets. Further, by understanding the mechanisms by which free-living organisms become disease-causing parasites we may better evaluate risks associated with the emergence of new pathogens. Also, our genomic data can be used to detect parasites in samples of microbe DNA from human guts; we aim to use this to determine whether common human parasites are associated with complex conditions like irritable bowel syndrome.