Project description

Antibiotic resistance is a threat to our future. The proliferation of multi-drug resistant bacteria as a result of our overuse of antibiotics means that, one day, even simple surgeries may go back to being prone to deadly infections. We desperately need new antibiotics and to do this we need new targets. DNA is at the centre of all life and we all know it as the double stranded DNA structure but it can also adopt other shapes. One of these is the four way junction (4WJ) and the presence of extended sequences in the bacterial genome called “inverted repeats” suggests that this may be a good target for new antibacterial agents that stabilise or disrupt its formation.

To date, their has been very little work carried out on the formation of 4WJ in the bacterial genome, so we aim to identify sequences that can form these structures and then show that compounds that we have designed and made can stabilise them. We will use a combination of biophysical and biochemical assays to probe these structures and solid and solution phase synthesis to generate new molecules that bind to them. We will study the effects of these compounds on bacteria, using methods developed here at UEA.

This project will develop a multidisciplinary scientist with expertise from chemical to cell biology. You will have, or expect to obtain a first class, 2(i) or equivalent Honours degree in Chemistry, Biochemistry, Pharmacology or a related area.

Informal enquiries are welcomed: Professor Mark Searcey (m.searcey@uea.ac.uk) or Dr Andrew Gates (a.gates@uea.ac.uk).

The Norwich Research Park Biosciences Doctoral Training Programme (NRPDTP) is offering fully funded studentships for October 2026 entry. The programme offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team.

This project has been shortlisted for funding by the NRPDTP. Shortlisted applicants will be interviewed on 3,4 or 5 February 2026.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/.

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.

To maximise accessibility and attract students from underrepresented groups to our programme we have introduced bespoke templates for applicant Personal and Research statements which will enable every applicant to fully represent themselves through providing suitable examples and evidence. These forms are on the NRPDTP website and must be used for these sections of the application form.

Entry requirements

At least UK equivalence Bachelors (Honours) 2:1. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

Funding

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership PhD DTP studentship. The studentship includes payment of tuition fees (directly to the University), a stipend to cover living expenses (2025/6 stipend rate: £20,780), and a Research Training Support Grant of £5,000pa for each year of the studentship.

References

Ivens, E.; Cominetti, M. M. D.; Searcey M. Junctions in DNA: underexplored targets for therapeutic intervention. Bioorg. Med. Chem. 2022, 69, 116897

Abdelhamid, A. S .A.; Gates , A. J.; Waller, Z. A. E. Destablization of i-motif DNA at neutral pH by G-quadruplex ligands. Biochemistry, 2019, 58, 245-259.

Beekman, A. M., Cominetti, M. M. D., Walpole, S. J., Prabhu, S., O’Connell, M. A., Angulo, J. & Searcey, M. Identification of selective protein–protein interaction inhibitors using efficient in silico peptide-directed ligand design. Chem. Sci. 2019, 10, 4502-4508.

Austin, M. J.; Hearnshaw, S. J.; Mitchenall, L. A.; McDermott, P. J.; Howell, L. A.; Maxwell. A.; Searcey M. A natural product inspired fragment based approach towards the development of novel anti-bacterial agents. MedChemComm 2016, 7, 1387-1391

Howell, L. A.; Bowater, R. A.; O’Connell, M. A., Reszka, A. P. Neidle, S, Searcey, M. The synthesis of small molecules targeting multiple DNA structures using click chemistry. ChemMedChem, 2012, 7, 792-804

Development of new antibacterial compounds in the fight against microbial resistance (SEARCEY_U26DTP)

Project description

Entry requirements

Funding

References