Project Outline

This project will generate new functional materials by combining advanced material science with synthetic biology. Specifically, de novo designed metallo coiled coils will be strategically incorporated into porous metal organic frameworks (MOFs). Ultimately designed materials could find applications in solar energy capture, bioremediation, catalysis, sensing and metal ion separation and recovery.

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. Most 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.[1] 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 solar energy capture, bioremediation, catalysis, sensing and metal ion separation and recovery. Applications which, for device fabrication, benefit from embedding such coiled coils within a porous material.

This project will introduce designed coiled coils and their complexes both within existing MOF architectures (see Figure),[5] and ultimately as the building blocks by which new MOFs are constructed.

This project is a collaboration between the Peacock and Champness research groups, bringing together expertise in protein design, synthesis and characterisation (Peacock) with advanced materials science (Champness). This powerful synergy will offer the student the opportunity to become expert in the broadest range of techniques and skills.

References

[1] 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.

[2] 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.

[3] Slope, L. N.; Daubney, O. J.; Campbell, H.; White, S. A.; Peacock, A. F. A., “Location Dependent Lanthanide Selectivity Engineered into Structurally Characterized Designed Coiled Coils“, Angew. Chem. Int. Ed., 2021, 60, 24473.

[4] Shah, A.; Taylor, M. J.; Molinaro, G.; Anbu, S.; Verdu, M.; Jennings, L.; Mikulska, I.; Diaz-Moreno, S.; Mkami, H. E. L.; Smith, G. M.; Britton, M. M.; Lovett, J. A.; Peacock, A. F. A., “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.

[5] Griffin, S.L.; Champness, N.R. “A Periodic Table of Metal-organic Frameworks” Coord. Chem. Rev., 2020, 414, 213295.

Techniques

Training and experience will be gained in protein design, synthesis and biophysical characterisation techniques including, but not limited to, native mass-spectrometry, ultraviolet-visible, fluorescence and circular dichroism spectroscopy, as well as the synthesis of materials (metal-organic frameworks) and small molecule components, including their purification. Characterisation by X-ray diffraction (both single crystal and powder), NMR and IR spectroscopy, mass spectrometry.