Chemical biology of cellular signalling using polyphosphate messengers

Different cells can communicate via chemical messengers, such as hormones and neurotransmitters, and the malfunction of cell-signalling pathways often underlies disease. Such 'first messengers' generally interact with a cell surface receptor, and small-molecule 'second messengers' subsequently carry this signal to internal effector proteins to coordinate a response. Professor Potter will use the techniques of chemical biology, employing synthetic and biological chemistry, to explore the application of tailored synthetic signalling tools in investigative biology. His prime focus is on messengers possessing multiple phosphate groups that dynamically mobilise cellular calcium, such as the cyclitol polyphosphate IP3, and also on newer signalling nucleotides such as cADPR, NAADP and ADPR, and the enigmatic higher inositol polyphosphates. Designing chemical tools for the modulation of these polyphosphates by changing molecular structure, in concert with other interdisciplinary techniques and as part of a process informed by structural biology, will provide both targeted tools for the interrogation of cell-signalling mechanisms and early leads for potential drug candidates.