Principal Supervisor: Professor Robin May, School of Biosciences
Co-supervisor: Dr Alan McNally, Institute of Microbiology and Infection
PhD project title: Understanding the evolution of virulence in Prototheca
University of Registration: University of Birmingham
Prototheca are a genus of pathogenic eukaryotic microbes that are associated with the plant surfaces and water. Penetrating injuries can introduce these organisms into the subcutaneous tissue where they can cause severe inflammation and, rarely, disseminated fatal disease. Protothecosis is a rare, though severe, disease of humans, but a relatively common cause of mastitis and enteritis in cattle worldwide.
Intriguingly, Prototheca have evolved relatively recently from a photosynthetic algal ancestor. However, almost nothing is known about the evolutionary steps that led them to become pathogens, nor the underlying virulence factors that allow them to evade the immune system and cause systemic infection in mammals.
This project will begin to investigate both of these questions by using a combination of pathogen genomics and cell biology to identify gene loss/gain events in this clade and correlating those with in vitro investigation of the innate immune response to these organisms. Specifically, we aim to determine the genetic and molecular steps by which this clade has evolved pathogenesis, with the ultimate aim of both a) learning more about fundamental evolutionary principles underlying the evolution of virulence and b) ultimately identifying novel targets that may have therapeutic potential in veterinary medicine.
- Deng et al, Mycopathologia. 2016 Aug 24 An Investigation of the Innate Immune Response in Bovine Mammary Epithelial Cells Challenged by Prototheca zopfii.
- Lass-Florl, C et al. Clin Microbiol Rev. 2007 Apr;20(2):230-42. Human Protothecosis
BBSRC Strategic Research Priority: Food Security
Techniques that will be undertaken during the project:
- Genomic/bioinformatics techniques to be used include de novo sequencing, genome assembly/annotation and comparative genome content analysis.
- Cell biology techniques to be used include a) in vitro analysis of chemotaxis, phagocytosis and cytokine release from primary human leukocytes and b) advanced microscopy and flow cytometry analyses of Prototheca morphology and behaviour.
Contact: Professor Robin May, School of Biosciences