The analysis of structural and affinity data of the pentameric ligand gated ion channels Glycine and Histamine in a drug discovery directed approach (360G-Wellcome-203751_Z_16_A)

The research focuses on protein gates in the brain that either inhibit or allow electrical signals to be passed on. To open these gates a specific molecule has to interact with the locking mechanism to unlock the gate and allow particles to flow through. These particles can be positively or negatively charged and depending on this charge can allow or inhibit the signal, respectively. Different gates exist to regulate the different processes these signals are activating. For example, one gate is known as the glycine receptor and this has roles in inflammation and chronic pain. Unlocking the glycine gate for the inflammation pathway could inhibit inflammation signals and decrease swelling. Our research is looking at how these gates are built and how different molecules interact in different ways to either keep the gate locked or to unlock it and allow the flow of particles. By understanding the structure of the gate and how molecules interact, drugs can be developed towards specific gates to relieve symptoms. As well as the glycine gate we also look at the serotonin, GABA, acetylcholine and histamine gates, all of which regulate different processes in the central nervous system.