The University of Bath is inviting applications for the following PhD project commencing as soon as possible.
Intended Supervisory Team:
- Dr Stefan Bagby, University of Bath, Department of Life Sciences (lead supervisor)
- Dr Sarah Tansley, University of Bath, Department of Life Sciences
- Prof Edward Feil, University of Bath, Department of Life Sciences
- Prof Neil McHugh, University of Bath, Department of Life Sciences
- Prof Justin O'Grady, Oxford Nanopore Technologies (subject to contract)
Project Overview:
Nanopore sequencing will be used towards improved clinical outcomes and better understanding of disease, including infections and triggers of autoimmune diseases, by providing much quicker and more detailed information than analytical methods currently adopted in clinical settings. Informed treatment of infections, for example, typically depends on culture screens, which take 48-72 hours. Using nanopore sequencing-based methods, one can identify the pathogenic microbe(s), including antimicrobial resistance data, within 6-8 hours (i.e. within a working day), and provide microbial genome sequences with associated detailed information for genome-level infection surveillance within 24 hours (1, 2).
The student will adapt and develop nanopore sequencing-based clinical metagenomics methods (1, 2) for a target cohort broadly comprising patients predisposed to infection, for example due to a chronic disease such as lung disease or due to medication (such as immunosuppressants administered to autoimmune disease patients). Defining the pathogens responsible for an infection, and their antimicrobial resistance characteristics, is important for antibiotic choice and, in some cases, for prognosis. In addition, testing for clearance of infection is crucial to reduce drivers of resistance; clearance of infection is currently assessed by culture or sometimes normalisation of blood markers.
One target cohort, chronic lung disease patients, may be colonised by bacteria, including mycobacterial species that are not covered by first-option antibiotics. Rapid, detailed information is therefore crucial for selecting the most appropriate antibiotic and for determining the duration of antibiotic administration, and consequently for antibiotic stewardship. Depending on the range of samples available, moreover, it may be possible to elucidate patterns in pathogen occurrence and antimicrobial resistance across different types of lung disease (e.g. bronchiectasis, cystic fibrosis, interstitial lung disease, chronic obstructive pulmonary disease).
Autoimmune disease patients will be another target cohort. Autoimmune rheumatic diseases occur in genetically susceptible individuals following an environmental trigger, frequently suggested to be an infection. In ANCA vasculitis, for example, Staphylococcus aureus nasal carriage has been linked to disease flares and worse treatment response. Nasal swabs from ANCA vasculitis patients will be sequenced and the organisms identified will be monitored with respect to treatment response and flare. This could lead to a larger study encompassing other diseases such as giant cell arteritis and connective tissue diseases (e.g. lupus and myositis), potentially helping to improve understanding of autoimmune disease triggers.
Hospital microbiology/immunology labs will be one source of patient samples (e.g. sputum, blood) as there is usually a surplus of sample once analytical procedures have been completed. Such samples are anonymised and untraceable, so ethical approval is not required; these types of samples will be useful in themselves and for proof of principle experiments. The second sample access route will Involve an application for ethical approval since this is required to access samples matched with clinical information like underlying diagnosis, age and antibiotic use.
The project will entail close collaboration with sponsor Oxford Nanopore Technologies (subject to contract), Miten Jain (UC Santa Cruz), and Robert Chapman (IMT1 Doctor, Intensive Care Unit, The Princess Alexandra Hospital NHS Trust).
Project keywords: antimicrobial resistance, autoimmune disease, clinical metagenomics, genome sequencing, infection, nanopore sequencing.
Candidate Requirements:
Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent). A master’s level qualification would also be advantageous.
Non-UK applicants must meet our English language entry requirement.
Enquiries and Applications:
Informal enquiries are welcomed and should be directed to Dr Stefan Bagby on email address [Email Address Removed].
Formal applications should be made via the University of Bath’s online application form for a PhD in Biochemistry.
More information about applying for a PhD at Bath may be found on our website.
Note: Applications may close earlier than the advertised deadline if a suitable candidate is found. We advise you to contact Dr Bagby for an informal discussion prior to applying and to submit your formal application as early as possible.
Funding Eligibility:
To be eligible for funding, you must qualify as a Home student. The eligibility criteria for Home fee status are detailed and too complex to be summarised here in full; however, as a general guide, the following applicants will normally qualify subject to meeting residency requirements: UK nationals (living in the UK or EEA/Switzerland), Irish nationals (living in the UK or EEA/Switzerland), those with Indefinite Leave to Remain and EU nationals with pre-settled or settled status in the UK under the EU Settlement Scheme). This is not intended to be an exhaustive list. Additional information may be found on our fee status guidance webpage, on the GOV.UK website and on the UKCISA website.
Equality, Diversity and Inclusion:
We value a diverse research environment and aim to be an inclusive university, where difference is celebrated and respected. We welcome and encourage applications from under-represented groups.
If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.