Sustaining Innovation Postdocs and Projects

Dr Andrew Heard

Molecular Sciences, Astex Pharmaceuticals and Chemistry, the University of Cambridge

Many attempts to use cryo-EM technique to determine structure are negatively impacted by the preferred orientation of studied macromolecules on the grid (flat molecules do not lay randomly on the surface). This results in a dataset with a highly anisotropic distribution of macromolecule projection images and adversely affects the quality of the reconstructed electrostatic potential map. The field of metal-organic chemistry has produced different polyhedral structures that encapsulate many different cargoes, including macromolecules. Therefore, we aim to encapsulate macromolecules in spherical metal-organic polyhedral cages, which will result in random orientations of the macromolecule relative to the grid surface.

This is a joint postdoctoral project between Astex and Prof. Jonathan Nitschke’s group at the Yusuf Hamied Chemistry Department of the University of Cambridge. We build on the experience of the Nitschke group, accumulated on building molecular cages and encapsulating different cargoes.

Recent publications:

Wu et al., A Diverse Array of Large Capsules Transform in Response to Stimuli. J. Am. Chem. Soc. 2023;

Wu et al., Systematic construction of progressively larger capsules from a fivefold linking pyrrole-based subcomponent. Nature Synthesis 2023;

Clark et al., A Double-Walled Tetrahedron with AgI4 Vertices Binds Different Guests in Distinct Sites. Angewandte Chemie 2023;

Lu et al., Enantioselective fullerene functionalization through stereochemical information transfer from a self-assembled cage. Nat. Chem. 2023;