At the very heart of Pharmacology is the need to understand the structures and functions of macromolecules such as proteins and DNA, and the exploitation of drug action at these macromolecular targets for the production of therapeutic benefits. The four members of this theme form a highly collaborative and cohesive group focused on this goal.
Edwardson and Henderson have worked together for a number of years on the study of biomolecules using atomic force microscopy (AFM). AFM enables the imaging of individual molecules under near-physiological conditions. Excitingly, a recently acquired fast-scan atomic force microscope allows near-real time imaging of macromolecular activity. Current areas of interest include the assembly and activation-induced structural changes in ionotropic receptors and ion channels, the molecular basis of polycystic kidney disease and of congenital generalized lipodystrophy, the structure of G-quadruplex DNA, and the use of DNA origami as a scaffold for use in the study of protein function and protein-DNA interaction. Murrell-Lagnado is interested in the structure, function and cell biology of the P2X family of membrane receptors. P2X receptors are cation channels that open on binding extracellular ATP and are widely distributed throughout all major systems in the body, playing a key role in afferent signalling, in the regulation of blood flow and the generation of inflammatory responses. Extracellular ATP signals tissue injury, sites of inflammation and cancers. P2X receptors are therefore involved in many diseases and are important targets for the development of new drug therapies. Rahman’s research interests include cellular calcium signalling, with a focus on the behaviour and functional regulation of intracellular calcium channels by second messengers such as IP3. He is particularly interested in their behaviour and regulation at the single molecule level. Rahman is also interested in rational design and development of small molecules that can be used to probe or modulate ion channels and also other signalling proteins.