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   School of Medicine

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  Dr K Wright  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

The diagnosis of orthopaedic infection remains difficult as there is no gold standard. Diagnosis is made in a multi-disciplinary setting based on clinical findings, blood results, microbiological cultures and histology. However, particularly in infection relating to orthopaedic implants, microbiological cultures are difficult to specifically diagnose and take time. Furthermore, contamination can lead to false positive results. Histological assessment of orthopaedic infection can be non-specific and difficult to differentiate from inflammatory joint disease such as rheumatoid arthritis. Genomic sequencing has become cheaper and with the introduction of Nanopore® sequencing, has become readily available in the clinic. The aim of this project is to assess whether genomic sequencing of bacterial DNA can be used in the diagnosis of orthopaedic infection. This is a portfolio study that is supported by the NIHR. Blood, tissue and fluid samples from patients with orthopaedic infection will have the DNA extracted. The extracted DNA should be checked for quality and quantity using standard laboratory techniques. Following sequencing, bacterial species can identified with software such as BLAST. In addition, it should be possible to obtain antibiotic profiles based on sequencing results. The number of bacteriae present in blood and tissue is likely to be small and processes will need to be optimised to obtain high sensitivity. Furthermore, specific laboratory methods will need to be developed to improve extraction of bacterial DNA in conjunction with optimised software algorithms. Ideally, processing is done whilst the patient is undergoing surgery and process time should be reduced as much as possible. Sequencing flow cells can be used multiple times and their use should be optimised to reduce cost. Sequencing results should be cross referenced with microbiological data, histology results and discussed at the local infection MDT were appropriate. There will also be an opportunity to evaluate histology and cross reference with previously obtained data. This project provides the opportunity to work closely with clinicians, patients and samples /data to address a pertinent clinical question that will likely lead to patient benefit. The successful applicant will be expected to communicate with patients and surgeons, take consent and obtain samples in the operating theatre. The studentship will be based at the RJAH Orthopaedic Hospital in Oswestry. However, there will be the occasional need to attend training at Keele University.

Please apply quoting reference PHAB2022.01 

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