About the Project
The DTP offers an interdisciplinary research training programme delivered by a consortium comprising the Universities of Bath, Bristol and Exeter, Cardiff University and Rothamsted Research, alongside six regional associate partners: Marine Biological Association, Plymouth Marine Laboratory, Swansea University, UCB Pharma, University of the West of England and SETsquared Bristol.
All SWBio DTP projects will follow a structured 4-year PhD model, combining traditional project-focussed studies with a taught first year which includes directed rotation projects.
+++ Studentships are available for entry in October 2021 - please see the ’Funding Notes’ below and https://www.swbio.ac.uk/programme/eligibility/ for information on eligibility +++
Lead supervisor: Dr Susanne Gebhard, University of Bath, Department of Biology & Biochemistry, email firstname.lastname@example.org https://researchportal.bath.ac.uk/en/persons/susanne-gebhard
Co-supervisors: Prof Jody Mason (Bath) and Dr Steven Porter (Exeter)
OVERVIEW OF THE RESEARCH:
Antibiotic resistance is one of the grand challenges faced by modern medicine, and tremendous efforts are invested in developing new treatments to slow its spread. One exciting approach is the development of anti-resistance drugs that do not themselves inhibit bacteria, but instead block resistance and reinstate the usefulness of our existing antibiotics.
Many resistance mechanisms are tightly regulated by the bacteria and only expressed in the presence of antibiotics. Dedicated signalling pathways detect the presence of drugs and transmit this information to the cell’s interior to activate gene expression. If signalling can be blocked, resistance can no longer be activated and the bacterium once again becomes susceptible to the antibiotic. In this PhD project, you will investigate the development and characterisation of peptide-based inhibitors of such a signalling pathway. As a member of the Gebhard lab, you will tap into over 10 years’ experience in signalling pathways that control antibiotic resistance in Gram-positive bacteria. Specifically, you will focus on histidine kinases of the BceS type. These proteins possess a coiled-coil structure at their core, which is known to be essential for their function. In an exciting interdisciplinary collaboration, you will work with the Mason lab, who have pioneered the use of peptide antagonists to disrupt coiled-coil protein function. This has had great success in the context of cancer and neurodegenerative disease, and is now ready to be applied to bacterial signalling.
You will begin with in silico analyses of protein and peptide sequences, to define the most promising starting point for inhibitor design. A combination of random and directed peptide screening approaches will identify functional antagonists, which you will take forward for biochemical characterisation. This will be supported by the Porter lab in Exeter, who are experts in bacterial kinase biochemistry. Antibiotic susceptibility and signalling assays will test the ability of your peptide antagonists to block resistance in living cells. Finally, by comparing endogenously produced to externally added peptides, you will begin to explore aspects of drug delivery, such as permeability to reach intracellular targets.
The supervisory team and international collaborators provide comprehensive expertise in this interdisciplinary project. You will find a supportive and stimulating environment to guide you through the challenges and rewards of this project. The conserved structure of histidine kinases and designability of peptide antagonists means that your results will be translatable to other systems, opening up a new avenue for combating resistance.
Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.
Informal enquiries are welcomed and should be addressed to the lead supervisor.
Enquiries about the application process should be addressed to email@example.com.
Formal applications should be submitted on the University of Bath’s online application form for a PhD in Biosciences: https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-DT01&code2=0005
Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section. You may apply for more than one project if you wish but you should submit a separate personal statement relevant to each one.
If you are an EU/EEA/Swiss national with settled or pre-settled status in the UK under the EU Settlement Scheme, please upload documentary evidence with your application.
More information about applying for a PhD at Bath may be found on our website https://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/.
The main categories of candidates normally eligible for 'Home' fees are:
Irish nationals living in the UK/Ireland
Applicants with settled or pre-settled* status in the UK under the EU Settlement Scheme
Applicants with indefinite leave to enter/remain in the UK
* must have lived in the UK/EEA/Switzerland continuously since September 2018.
If you do not qualify for ‘Home’ fees, you may be considered for an international student fee discount equivalent to the difference between ‘Home’ and ‘Overseas’ fees.
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