Beta-lactams are the most widely prescribed antimicrobial class worldwide. Resistance is primarily caused when bacteria produce beta-lactamase enzymes, of which there are many different types. There are several clinically available beta-lactamase inhibitors; chemicals which block beta-lactamase mediated resistance, therefore allowing a partner beta-lactam to regain function. Key examples are amoxicillin/clavulanate and piperacillin/tazobactam, which are mainstay combinations in the UK; ceftazidime/avibactam and meropenem/vaborbactam, which have recently been introduced into clinical practice; and several experimental inhibitors in various stages of development.
The aim of this project is to investigate mechanisms of resistance to these different combinations in two key human pathogens: Escherichia coli and Klebsiella pneumoniae. You will investigate whether different clinical isolates have different potentials for generating resistance, and identify the mechanisms involved. You may use structural biology and enzyme analysis of resistance is a property of the beta-lactamase; you will use functional genomics approaches to study mechanism of resistance if chromosomal. You will benefit from access to clinical, animal and environmental isolates from the UK and Thailand, collected as part of two large consortium projects.
By developing novel flow cytometry approaches, you will also investigate whether resistance comes with a measurable fitness cost, and if different resistant variants of different background strains has a greater or lesser fitness, suggesting those backgrounds most likely to yield successful resistant strains that might circulate in the population.
The project will suit someone with a microbiology, molecular biology or biochemistry background, who wants to work in an inter-disciplinary team to understand this important clinical problem
Potential applicants interested in further information are encouraged to contact Professor Matthew Avison at [email protected]
Benefits of joining the Medical Research Foundation National PhD Training Programme in AMR Research.
• All PhD projects will be based within interdisciplinary research consortia funded by the UKRI Cross-Council AMR Initiative.
• All students will have access to enhanced training opportunities including residential skills and training courses, cohort-building activities, and annual conferences. All are designed to expose students to a range of discipline-specific languages and interdisciplinary research skills, which are essential for enabling them to thrive as multidisciplinary AMR researchers.
• PhD students will undertake a fully-funded 3-month interdisciplinary AMR project allowing them to work outside of their primary research area or an elective placement in industry, publishing, media, policy development or in AMR-relevant charities and organisations.
• All Medical Research Foundation-funded PhD students will also be part of a wider cohort of 150 PhD students from across the UK who are also studying AMR. The cohort will have access to a bespoke, innovative online learning environment, which will facilitate peer-to-peer networking, question setting and mentoring.
Further information can be found on our website: https://www.bristol.ac.uk/cellmolmed/study/postgraduate/amr/
Applicants must ensure that they meet the eligibility requirements of the University of Bristol. To qualify for Home tuition fee status, you must be a UK or EU citizen who has been resident for 3 years prior to commencement. Please note that overseas students not eligible for Home (UK/EU/EEA citizens) tuition fee status will be eligible for funding through this Programme but the student must pay the difference between the annual Home tuition fee and the tuition fees required for overseas students. Overseas students should be able to demonstrate adequate financial support to cover the difference between the Home/EU fee and the overseas fee. Applicants are also required to meet the University of Bristol’s English language requirements.
As part of your application, you need to choose: Faculty of Life Sciences under the ‘Faculty’ section, and Cellular and Molecular Medicine 4-year PhD programme under the ‘programme choice’ section. Additionally, under ‘funding’ and ‘Research Details’ section, please indicate that you are applying for a Medical Research Foundation National PhD Training Programme in AMR Research funded project and give the project title and names of the supervisors.