CATSIG: Synthesis and study of catalytic signalling systems to create vesicles that mimic cell sensing and signalling

A critical feature of complex biological systems is the compartmentalisation provided by lipid bilayer membranes. This separates the inside and outside solutions and allows otherwise incompatible chemical processes and networks on the interior and exterior to co- exist independently. However, it is critical that extracellular molecules, such as hormones, nutrients and pathogens, can change the intracellular chemistry - and this is achieved by signalling across the cell membrane, usually via membrane-spanning proteins, which trigger a cascade of reactions which both amplify and transduce the original signal so that the cell can respond appropriately. Vesicles are simplified analogues of cells, and have the potential to store, amplify, transduce and communicate information in the same way, and this proposal aims to functionally mimic the cellular response with entirely synthetic systems. The aim is to couple an external molecular recognition event with an internal catalytic process using a novel transmembrane signal transduction pathway. Vesicles are already used in drug-delivery applications, but there is huge potential for responsive vesicles - those that can react in a specific and targeted way to an external signal such as a molecular binding event - which could be used in targeted drug delivery, such as the catalytic activation of a pro-drug for controlled-release applications. Furthermore, multivalent vesicles that are capable of efficient transduction of chemical information will provide a platform for the construction of biocompatible interfaces for communication with cellular systems for sophisticated sensing applications and diagnostics.