PhD Studentship: Design of Metallo Coiled Coil MRI Contrast Agents

This PhD project will develop a new class of magnetic resonance imaging (MRI) contrast agent. MRI is an essential tool for medical diagnosis. Contrast agents (CAs) play a crucial role in improving the images obtained, and hence patient outcomes. Most clinical MRI contrast agents are based on gadolinium. However, gadolinium’s toxicity is a recognised problem for patients and the environment. This project takes inspiration from biology to design, synthesize and characterise a new class of MRI contrast agents, based on miniature artificial protein scaffolds, which have the potential to be more effective, safer and environmentally sustainable than current Cas. 

The project builds on a long-term collaboration between the Peacock and Britton groups, bringing together expertise in peptide and protein design, synthesis and characterisation (Peacock) with MRI application and development (Britton). We have previously shown that when coordinated to gadolinium, these complexes offer superior properties to current clinical agents[1,2]. More recently, we reported for the first time that, when coordinated to these ligands[3], copper, which has previously overlooked in MRI contrast agent design, performs better than current CAs, while offering other significant biological advantages. The project will develop, using automated peptide synthesis methods, new miniature protein-inspired ligands, based on coiled coils, for use as novel MRI contrast agent. This project will be ideally suited to students that are interested in MRI, inorganic chemistry and/or synthetic biology. 

Training will be given in (computational) peptide design, synthesis, characterisation, metal binding evaluation and MRI, providing students the opportunity to become expert across the broadest range of techniques and skills. 

Applications from candidates with a first degree (with a minimum 2.1 degree or above, or equivalent) in chemistry, or a related subject, are strongly encouraged to apply.

The University is a family-friendly employer and the School of Chemistry welcomes flexible working to suit family or other commitments. The University has on-campus childcare facilities. The School of Chemistry holds an Athena SWAN Bronze Award in recognition of its work in promoting women’s careers in STEM subjects in higher education. The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC- funded doctoral training partnership between the Universities of Warwick, Birmingham, Aston, Harper Adams and Leicester. It delivers innovative, world-class research training across the Life Sciences to boost the growing Bioeconomy across the UK.

We advise all interested applicants to contact us via email (m.m.britton@bham.ac.uk; a.f.a.peacock@bham.ac.uk) for more information. Formal applications will need to be made https://www.birmingham.ac.uk/schools/chemistry/phd/apply.aspx and by completing the MIBTP notification form (https://warwick.ac.uk/fac/cross_fac/mibtp/phd/application/#Application)

References:

[1] Berwick et al “De Novo Design of Ln(III) Coiled Coils for Imaging Applications” J. Am. Chem. Soc., 2014, 136, 1166.

[2] Berwick et al “Location dependent coordination chemistry and MRI relaxivity in de novo designed lanthanide coiled coils” Chem. Sci., 2016, 7, 2207.

[3] Shah et al “Design of the elusive proteinaceous oxygen donor copper site suggests a promising future for copper for MRI contrast agents“, Proc. Natl. Acad. Sci., USA., 2023, 120, e2219036120.

Funding Details

Additional Funding Information

The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC- funded doctoral training partnership between the Universities of Warwick, Birmingham, Aston, Harper Adams and Leicester. Studentships include: Full tuition fees, a tax free annual stipend (in academic year 2024-25 this was £19,237), a travel/conference budget, a generous consumables budget, use of a MacBook Pro for the duration of the programme. To check your eligibility to apply for this project please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/phd/application/#Eligibility

Advert information