Nucleation and Polymorphism in Pharmaceutical and Biological Systems

A fully-funded, three year PhD studentship is available in the groups of Fabio Nudelman and Simon Parsons at The University of Edinburgh to study how crystal nucleation can be manipulated to control polymorphism in biological and pharmaceutical systems.

Biomineralisation is the process by which organisms produce bones, shells, teeth and other mineral structures. Even unicellular species of plankton can produce shell-like structures using calcium carbonate. Generally, organisms use specialised proteins and polysaccharides to control the nucleation, growth and polymorph type (i.e. aragonite or calcite in the case of calcium carbonate) of biogenic crystals. Many such organisms live in oceans at depths of many hundreds or even thousands of metres, where pressures can reach hundreds of atmospheres. The macromolecules have a high degree of conformational flexibility, and their structures are likely to be affected by pressures in this range. In this project we will explore how the interplay between pressure and the macromolecules can influence nucleation, morphology and polymorph formation.

Amongst the most important techniques to be used in this study is cryo-transmission electron microscopy (cryo-EM), which was the subject of the Nobel Prize for Chemistry in 2017. This enables imaging of crystallisation processes, showing, for example, that clustering of initial amorphous aggregates can lead to formation of crystals [see, for example, Walker, Marzec & Nudelman, Angew. Chem. (2017), 56, 11740]. Polymorphism and control of crystallisation is of critical importance in pharmaceuticals, because different solid forms have different solubilities and varying bioavailability. In this project we will also apply Cryo-EM to study the crystallisation of pharmaceuticals and other simple organic compounds to reveal how different amorphous and crystalline forms complete and evolve over the course of crystal growth.

Applicants must have or expect to obtain a 1st class or an upper 2nd class honours degree (or equivalent) and meet the EPSRC residency requirements, which restrict awards to UK and EU nationals. Informal enquiries should be addressed to [Email Address Removed] or [Email Address Removed], with applications made through the EUCLID system as outlined at http://www.chem.ed.ac.uk/studying/postgraduateresearch/applications-and-entry-requirements.

Applications will be considered until an excellent candidate has been identified.

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