A combined statistical and high-throughput experimental approach for the predictive crystallization of small molecules.

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This PhD CASE award with AstraZeneca will focus on the development of our ground breaking high throughput Encapsulated Nanoscale Crystallization technology. With the aim to control the solid form of new drug-like molecules to have improved bioavailability and physical properties. Previous work by the Newcastle group has resulted in the development of ENaCt, providing the first platform technology for automated nanoscale crystallization. In this project I will work with the crystallography group of AstraZeneca, headed by Dr McCabe, to further develop the technique and enhance the high-throughput Encapsulated Nanoscale Crystallization technology protocols for the crystallisation of drug-like molecules, a key step in new drug development. Working with a focussed set of drug-like molecules, under the supervision of Drs Hall and Probert, I will refine the ENaCt methodologies to provide optimised crystallisation conditions for molecules based on their molecular properties. Through the use of high-throughput robotics I will develop automated work flows for both experimental setup and outcome analysis. Working with Dr Heaps I will implement enhanced experimental design that will allow the application of statistical analysis to the outcomes with the final aim of constructing a predictive crystallisation model in which experimental conditions can be deduced from molecular properties, an as yet unaddressed challenge in the field. With these tools in hand I will apply these methods to early stage drug molecules. Through the investigation of their crystal structures I will design synthetic modifications to improve solubility profiles. This will bring the consideration of bioavailability much earlier in the drug development process thus decreasing drug failure rates and speeding time to market. I will work as part of a cohort of PhDs/PDRAs in the Johnson and Crystallography laboratories. My roles will include: Developing and validating methods, and automated tools for the crystallisation of small quantities of complex small molecules.Establishing novel methods for measuring the success rates of automated crystallisation methods.Development of predictive algorithms that maximise the success rates of crystallisation experiments