Genomic, proteomic and microbiomic approaches to understanding the biology and pathogenesis of anaerobic protozoa

Protozoan parasites infect ~2 billion people worldwide and are responsible for the sickness of hundreds of millions. A number of these parasites colonize oxygen-poor (anaerobic) environments in the human body such as the gastrointestinal and urogenital tracts. Most of these organisms are understudied and their genomes, cell structures, and roles in human microbiomes remain poorly understood, despite their high prevalence in both affluent and developing-world populations. Using powerful high-throughput genome sequencing, high-resolution mapping of whole cellular 'proteomes' and sophisticated computational analyses, we are addressing how these anaerobic protozoa: (i) live without oxygen, (ii) parasitize humans, and (iii) influence human gastrointestinal health. We will generate 'parts lists' for prevalent protozoan parasite cells and identify the genes that allowed them to live without oxygen, parasitize their hosts and cause disease. The roles of these organisms in the human gut and disease will be investigated using novel computational methods applied to genomic data obtained from faecal samples from hundreds of individuals from four distinct populations worldwide. There are several of potential practical benefits of the proposed research. The species examined include common human gut parasites and close relatives of serious human pathogens; revealing unique aspects of their biology will help identify new drug targets and other interventions. 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. Our genomic data can also be used to detect and monitor parasites in DNA samples extracted from human feces; we will use this approach to investigate the roles these parasites in diseases.