Dr Emmanuel Saridakis

New crystallization strategies for structure-guided pharmacological development – large biological assemblies for rna metabolism

The elucidation of three-dimensional structures of molecular machines that control cellular physiology is necessary for the understanding of the mechanisms of life and for the development of rational screening tests for pharmaceutical applications. Due to the large size of these biological entities and the high resolution which is sought, X-ray crystallographic structure determination is the method of choice. Obtaining crystals of biological complexes however remains often difficult and is the bottleneck to this method. In this project, we will explore new crystallisation strategies and their capacity to be automated with an aim to enhance the likelihood and speed of obtaining crystals of sufficient quality for structure determination. We will apply these strategies to the specially difficult case of complex molecular motors involved in RNA metabolism, some of which are pharmacological targets of great interest. This project has wide application potential for academia (discovery of new biological operating mechanisms), technology (new crystallisation kits) and pharmaceutics (targetted virtual screening).