About the Project
Since MRI’s first clinical applications nearly thirty years ago, MRI has become an essential tool for clinical diagnosis. Image contrast is routinely enhanced by the use of a contrast agent (CA), with the overwhelming majority based on complexes of gadolinium, and more recently manganese.
However, current MRI CAs are limited by their small size (limits relaxivity, MRI efficiency) and inability to interact with biomolecules in a targeted fashion. In contrast, proteins satisfy both of these limitations, and thus, the goal of this project is to replace the ligands associated with traditional MRI CAs, with protein ligands.
Preliminary results have found that gadolinium complexes of miniature coiled coil protein scaffolds display superior MRI contrast capabilities compared to the traditional small molecular complexes currently employed in the clinic. This project will build on these findings, by engineering similar gadonlium (and manganese) sites into small proteins such as the family of knottin proteins, and larger assemblies with appropriate targeting opportunities.
This project builds on a long-term collaboration between the Britton and Peacock groups, bringing together expertise in peptide and protein design, synthesis and characterisation (Peacock) with MRI development and application (Britton). This powerful synergy will offer the student the opportunity to become expert in the broadest range of techniques and skills.
Funding Notes
This studentship is competition funded by the BBSRC MIBTP scheme: http://www.birmingham.ac.uk/research/activity/mibtp/index.aspx
Deadline: January 6, 2019
Number of Studentships available at the University of Birmingham: 18
The 2019/20 Stipend is expected to be £14,999 per annum (plus £850 travel allowance in year 1, and a laptop)
The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC-funded doctoral training partnership between the Universities of Warwick, Birmingham and Leicester. It delivers innovative, world-class research training across the Life Sciences to boost the growing Bioeconomy across the UK.
To check your eligibility to apply for this project please visit: http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/
References
[1] Berwick, M. R.; Lewis, D. J.; Pikramenou, Z.; Jones, A. W.; Cooper, H. J.; Wilkie, J.; Britton, M. M.; Peacock, A. F. A. “De Novo Design of Ln(III) Coiled Coils for Imaging Applications” J. Am. Chem. Soc., 2014, 136, 1166.
[2] Berwick, M. R.; Slope, L. N.; Smith, C.; King, S. M.; Newton, S. L.; Gillis, R; Adams, G.; Rowe, A.; Harding, S.; Britton, M. M.; Peacock, A. F. A. “ Location dependent coordination chemistry and MRI relaxivity, in de novo designed lanthanide coiled coils” Chem. Sci., 2016, 7, 2207.
[3] V. C. Pierre, et al., J. Biol. Inorg. Chem., 2014, 19, 127.
[5] Zastrow, M.; Peacock, A. F. A.; Stuckey, J.; Pecoraro, V. L. “Hydrolytic Catalysis and Structural Stabilization in a Designed Metalloprotein” Nature Chem., 2012, 4, 118.
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