Anaerobic eukaryotic microbes and the human microbiome: a genomic and metagenomic study

Protozoan parasites infect literally billions of people worldwide each year, and are responsible for the deaths of millions. Many of these parasites colonize oxygen-poor environments in the human body such as the gut and urogenital tract. Most of these species are understudied and their basic molecular biology and roles in the human 'microbiome' are poorly understood, despite their high prevalence in both affluent and developing world populations. Using powerful high-throughput next-generation genome sequencing approaches and sophisticated computer-based analyses, we will address how select groups of protozoa: (i) adapted to life without oxygen, (ii) acquired the ability to parasitize humans, and (iii) influence the healthy and diseased human gut. We will explore how these species have acquired new biochemical pathways suited to low-oxygen habitats and investigate other ways in which the genomes of single-celled parasites have changed to allow them to live within their hosts. The roles of a number of these organisms in the human gut will be investigated using novel computational methods applied to DNA-sequence data obtained from gut samples, both from healthy subjects and from patients suffering from inflammatory bowel disease (IBD). There are several potential practical benefits of this project. Our examinations of common human gut parasites and relatives of serious human pathogens will reveal unique aspects of their biology that could help identify new drug targets. 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 DNA sequence databases can also be used to efficiently detect parasites in fecal samples. Finally, our research has the potential to reveal links between the whole gut microbiome and human health that would have been impossible to discover previously, when the protozoan part of the microbiome had not been considered.