I studied Medicinal Chemistry at St Andrew’s and spent my industrial placement year in formulation at AkzoNobel (the Netherlands), followed by an MChem project in organocatalysis. Since then I have done several internships in organic chemistry, at Syngenta (Switzerland) and Medichem Manufacturing (Malta). Having particularly enjoyed a course in chemical biology during my degree, I became interested in using my chemical skills to solve biological problems, and was particularly interested in the interdisciplinary nature of this PhD project.
Extracellular signalling is a vital means for cells to communicate with each other, respond to their environment, and ultimately form functioning tissues. Signalling proteins bind to cell-surface receptors triggering cascades that lead to changes in cell behaviour. Critically, this signalling is concentration dependent with the clustering of receptors increasing signal potency. In this project, I will be designing new chemical techniques to probe this clustering process in precise detail, by creating polymer-protein conjugates that present multiple protein ligands in defined architectures to cells. By doing so, I will be able to identify the optimal orientation, arrangement, and valency of ligands needed to activate signalling, providing unprecedented understanding of this key biological phenomena. To do this, I need to develop new protein modification chemistries that selectively target protein N-termini irreversibly. Though a number of chemistries have previously been reported for targeting N-termini, selectivity is either incomplete or comes at the cost of stability. I will then be able to synthesise polymer-protein arrays via controlled radical polymerisations, and use these to correlate polymer architecture to intracellular signalling activation and persistence.