A novel mechanism for phenotype variation in Bordetella pertussis investigated by nanopore DNA sequencing and functional genomics
HYPOTHESIS: This project will use nanopore DNA sequencing and functional genomics approaches to test the hypothesis that B. pertussis generates phenotypic diversity via diversity in genome arrangement among strains. In so doing, the project could define a novel mechanism for generating phenotypic diversity in an important microbial pathogen.
BACKGROUND: B. pertussis is a Gram-negative bacterium that causes whooping cough, an infectious disease that is resurgent in many countries1. B. pertussis is regarded as genetically monomorphic, a view supported by genome sequencing that reveals very low levels of DNA/gene content diversity among B. pertussis strains2. However, the short read sequencing used originally could not produce closed (complete) genome sequences for B. pertussis strains due to high levels of repetitive sequences in these bacteria.
More recently, we have used long read DNA sequencing to produce closed genome sequences for several B. pertussis strains. This revealed that while the DNA content of strains was highly conserved, genome arrangement was highly variable among strains. The chromosomal location of genes could thus be highly variable between strains and this could affect genome-wide gene expression profiles. This may explain observations in which strains identified as nearly identical on the basis of DNA content behave differently in various in vitro assays.
PROJECT: To test the hypothesis, the long read capability of Oxford Nanopore Technologies’ MinION™ and PromethION™ DNA sequencing devices will be exploited to define the spectrum of genome arrangement diversity among B. pertussis, establishing a role for such technologies in the investigation of microbial genome architecture. The effect of genome arrangement on gene expression profiles and, in turn, phenotype will be investigated using functional genomic approaches.
TRAINING: The project will provide broad, multidisciplinary training across wet lab and dry lab methods, including an array of bioinformatics skills and cutting edge approaches in genomics. The project will also benefit from support from Oxford Nanopore Technologies and the worldwide MinION™ Access Programme online research community that the company has nurtured.
The successful candidate will be awarded a highly competitive PhD studentship which will cover their full Home/EU tuition fees, training support fee of £1,000/annum and a tax-free stipend of £14,057/annum (15/16 rate) for 3.5 years. This funding will be covered by the University of Bath Research Studentship Account (Science ) and by Oxford Nanopore Technologies.
He/She will be expected to start their PhD in October 2016.
Please note: overseas students are NOT eligible for this studentship.
1. Jakinovich A & Sood SK; Pertussis: still a cause of death, seven decades into vaccination. Curr Opin Pediatr 26, 597–604 (2014)
2. Belcher T & Preston A; Bordetella pertussis evolution in the (functional) genomics era. Pathogens and Disease 73, (2015) ftv064. doi: 10.1093/femspd/ftv064
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FTE Category A staff submitted: 24.50
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