Primary Supervisor: Dr Anna Peacock, School of Chemistry
Secondary supervisor: Ruchi Gupta
PhD project title: Peptide hydrogels for bioremediation and lanthanide separation
University of Registration: University of Birmingham
De novo designed miniature protein scaffolds are increasingly being investigated as novel ligands for metal ion coordination, as they offer many of the advantages of a native protein matrix, but without many of their limitations. The majority of such miniature de novo designed proteins are based on coiled coils or helical bundles, based on the alpha-helix building block, as these are more amenable to predictable design. Efforts have historically been directed towards the coordination of biological metal ions to mimic both structurally and functionally native metal ion sites in Nature. However, more recently there has been interest in the coordination of metal ions which do not feature commonly in biology, and this has led artificial metallo proteins with properties beyond the repertoire of Biology, including for potential use as MRI contrast agents.[2-4] Notably, these offer exciting opportunities for bioremediation as well metal ion separation. In fact there is much interest in the separation of the lanthanide ions, and preliminary results suggest that the coiled coil ligand could be successfully employed in this regard. However, for device fabrication, the immobilisation of these metal binding coiled coils is required.
This project will develop coiled coil hydrogels capable of metal ion binding and associated function. Their incorporation in hydrogels can enable multiplexed measurements, due to the opportunity to introduce arrays of different (metallo) coiled coils, each with differing metal ion selectivity or associated chemical property. Another important benefit of hydrogel waveguides being that they allow label-free measurements.
Figure 1 Cartoon representation of a miniature designed metallo coiled coil, featuring a Ln(III) ion bound within the core.
This project is a collaboration between the Peacock and Gupta research groups, bringing together expertise in peptide and protein design, synthesis and characterisation (Peacock) with hydrogel functionalization and device fabrication (Gupta). This powerful synergy will offer the student the opportunity to become expert in the broadest range of techniques and skills.
- 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.
- 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.
- 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.
- Slope, L. N.; Hill, M. G.; Smith, C. F.; Teare, P.; de Cogan, F. J.; Britton, M. M.; Peacock, A. F. A. “Tuning Coordination Chemistry Through the Second Sphere in Designed Metallocoiled Coils” Chem. Comm., 2020, 56, 3729-3732.
- R. Gupta, N.J. Goddard, Leaky Waveguides (LWs) for Chemical and Biological Sensing − A Review and Future Perspective, Sensors and Actuators B, 2020, 322, 128628
BBSRC Strategic Research Priority: Renewable Resources and Clean Growth: Industrial Biotechnology& Understanding the Rules of Life: Structural Biology
Techniques that will be undertaken during the project:
Training and experience will be gained in protein design, synthesis, biophysical characterisation techniques including, but not limited to, gel electrophoresis, ultraviolet-visible, fluorescence and circular dichroism spectroscopy, as well as hydrogel formulation and characterisation. Equally, the student will receive basic training in bioconjugation, and fabrication and characterisation of hydrogel leaky waveguides (LWs). The characterisation of hydrogel LWs will provide exposure to optical instrumentation, and the student will build skills in image processing and data analysis.
Contact: Dr Anna Peacock, University of Birmingham