Life in the nucleus, the genomic basis of energy exploitation by intranuclear microsporidia

We are inviting applications for this PhD studentship to commence October 2012. For eligible students the award will cover UK/EU tuition fees and an annual stipend (in 2011/12 this was £13,590 for full-time students, pro rata for part-time students) for three years.

This studentship will be funded by the College of Life and Environmental Sciences and Centre for Environment, Fisheries & Aquaculture Science (CEFAS). Successful applicants will benefit from working within a lively research environment within Biosciences (Streatham Campus, Exeter) at the College of Life and Environmental Sciences, University of Exeter.

Supervisors:
Dr Bryony Williams (University of Exeter) [Email Address Removed]
Dr Grant Stentiford (CEFAS) [Email Address Removed]

Microsporidia are a diverse group of obligate intracellular parasites of a broad range of animals. Before the AIDS pandemic, microsporidian infections in humans were rare. Now, however, microsporidia are frequently cited as one of the most common microbes associated with AIDS-related diarrhea. The most common human-infecting microsporidian is E. bieneusi, which is phylogenetically nested within the Hepatospora/Enterocytozoon clade of marine microsporidia, and its most close relative is Enterospora canceri, a parasite of the edible crab. This clade is a key taxon for understanding microsporidian evolution and pathogenicity. Firstly it contains the most common human-infecting microsporidian, and additionally because E. bieneusi is an important cell for understanding eukaryotic reductionism. Microsporidia have lost all mechanisms of oxidative phosphorylation, resulting in reduced mitochondria and a reliance on a combination of glycolysis and host ATP for energy. E. bieneusi, however has taken this reductionism a step further, and genome studies show that it has lost pathways associated with glycolysis making it utterly reliant on its host for energy, likely via ATP import from the host cytoplasm. Surprisingly, its close relative Enterospora canceri lives, not in the cytoplasm where ATP is available, but exclusively in the nucleus of its host. Given the close relationship between E. canceri and E. bieneusi and the potential loss of glycolytic pathway in E. canceri, a key question relates to how the crab parasite gains energy. Furthermore the presence of a glycolytic pathway in the closely related Hepatospora, provides a unique opportunity to investigate when glycolysis was lost is the evolutionary history of the Enterocytozoon clade.

This studentship proposes to exploit environmental samples gathered on CEFAS cruises and use Illumina HiSeq to sequence the genomes of Enterospora canceri and Hepatospora erocheir to address the following questions:
• What is the genomic basis of survival of Enterospora canceri in the energy poor intranuclear environment?
• When did the Enterocytozoon/Hepatospora clade lose its glycolytic pathway and is this a unique loss associated with infection of humans?

This will involve the generation of next generation sequence data (Illumina) genomic data mining and molecular biology methods such as DNA and RNA extraction, PCR, sequencing, protein expression and microscopy.