Supervisors; Prof Christopher Dowson, Prof Chris Schofield
This project will involve the combination of biochemical assays, design, synthesis and testing the effectiveness of new inhibitors inspired by the mode of action of β-lactams. Importantly, we aim for these to be resilient to resistance mediated by β-lactamases and alterations to penicillin binding proteins (PBPs) typically conferring resistance. This builds upon (i) extensive structural/biophysical analyses employing both solution and crystallographic methods, (ii) developing mechanistic work on PBPs and β-lactamases, (iii) work extending over several decades aimed to developing new types of PBP and β-lactamase inhibitor working either via acylation or as ‘transition state’ analogues (ACIE, Angew. Chem. Int. Ed, 2017, 56, 3862; Chemical Science, 2017, 8, 928; Nature Communications, 2016, 7, 12406).
The student will extend this work by developing boronates and other types of inhibitor which mimic high energy intermediates in PBP catalysis. The work will involve both design of compounds via analysis of crystallographic data, synthesis of compounds and depending on the interests of the student involvement in assays and solution based biophysical analyses employing techniques such as NMR and SPR. The project will provide training in cutting edge synthetic and chemical biology techniques, enzymology and microbiology. The successful candidate will be also able to undertake additional training opportunities and local student cohort activities available to MRC or EPSRC Doctoral Training Programme students.
Potential applicants interested in further information are encouraged to contact Professor Christopher Dowson [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 Warwick. 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 Warwick’s English language requirements.
As part of your application, you need to Identify that the School of Life Sciences will be your primary host and funded by Medical Research Foundation National PhD Training Programme in AMR Research http://www.bris.ac.uk/cellmolmed/study/postgraduate/amr/
. Additionally, under the ‘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. For admissions enquiries, please contact [email protected]