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PhD Studentship: Development of a Physiologically Relevant Platform to Inform Clinical Practice and Limit Antimicrobial Resistance in Orthopaedic Implants

University of Birmingham - School of Chemical Engineering

Qualification Type: PhD
Location: Birmingham
Funding for: UK Students, EU Students, International Students
Funding amount: Please see funding details below
Hours: Full Time
Placed On: 14th November 2023
Closes: 4th January 2024

Antibiotics are a cornerstone of modern medicine, and as well as treating infections, are crucial for clinical success in many operations including orthopaedic implants. However, antimicrobial resistance is a growing global health emergency. The World Health Organisation’s “Global Action Plan (GAP) on Antimicrobial Resistance” emphases awareness, education, and prevention, as well as the need for optimisation of current antimicrobial therapies. As such, informing clinical practice of optimal dosing regimes, concentrations and combinations of existing antibiotics as well as novel antimicrobial strategies is a strategic area of focus [1]. Nonetheless, the available literature has been focused on single molecules or combinations of well-known antibiotics without fully recognising the long-term effect of new bactericidal elements (e.g. silver) in conventional regimes.

Novel antimicrobials such as silver or copper are arising across healthcare applications to tackle AMR, however, recent studies have shown that combinations of these elements and current antibiotic practices can result in increased resistance development in vitro [2]. This disregard of novel technologies is further compounded by the limitations inherent to most used methods available to evaluate antimicrobial effectiveness. Only recently has the microbiology community recognised the critical role fluid flow and surface mechanics play in the survival of bacteria in natural environments [3]. Thus, static microtiter assays lack clinical relevance, increasing the potential for antibiotic misappropriation. Considering this, utilising bioreactors has the potential to provide more physiologically relevant and accurate infection models, improving the predictive value of current practices. Consequently, immediate actions against AMR should be focused on optimising antibiotic and antimicrobial treatments through clinically relevant models.

This PhD will develop a physiologically relevant platform to inform orthopaedic clinical practise with the aim of limiting AMR. For this purpose, the experimental plan will be focused in four principal areas:

  • Ascertain the effectiveness of antibiotic and antimicrobial mixtures, dosing and regimes on the short term and long-term resistance development of an array of clinical and laboratory strains of both Gram positive and negative bacteria typically associated with orthopaedic implant infections.
  • Unravel the phenotypic and genetic mechanisms behind the observed changes in resistance.
  • Modification of an existing bioreactor set up to create a physiologically relevant infection model for both planktonic bacteria and orthopaedic device surfaces colonised with early-stage attached bacteria and fully formed biofilms.
  • Engage with healthcare experts and regulators to optimise current practices.

About your supervisors:

Dr Sophie C. Cox is a Lecturer in the School of Chemical Engineering with the vision to improve patient quality of life by innovating new medical devices with unprecedented functionality. These translational activities are underpinned by basic science focused on understanding the biological response to biomaterials with particular attention on osteogenesis and infection.

Dr Tim Overton is a biochemist and molecular microbiologist who is interested in applying molecular biology and single-cell techniques to understand and develop bioprocesses. He is active in microbial flow cytometry research and collaborates widely to develop new methods of answering fundamental questions on a single-cell level.

Dr. Victor M. Villapun, Research Fellow, main interests lay on medical device functionalisation to limit bacterial colonisation and resistance development while enabling guidance of the wound healing process.

Funding Details

Details on eligibility and funding can be found at the UoB intranet (https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx) and the main MIBTP application site (https://warwick.ac.uk/fac/cross_fac/mibtp/)

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