Fellow

Andrew Tinker is an outstanding clinician scientist who has made major contributions to the field of heterotrimeric G-protein signalling and how the structure of K+ channels is related to their function. His work on the Galpha subunit solved the problem of how activation of G proteins achieve specificity. It was known that the Gbetagamma subunit can activate several ion channels and second messengers. He identified that the alpha subunit is critical to determine the selectivity of this process i.e. why one G-protein coupled receptor (GPCR) activates one pathway and a second activates an alternative pathway whilst releasing the same Gbetagamma subunit. In addition, he has shown why there are a number different Gi\o alpha isoforms: different receptors can selectively activate different members of this family and thus have distinct signalling consequences. Furthermore the combination of agonist, receptor and G-protein determine the dynamics of the response. These are fundamental observation relevant to many signalling processes, such as those involved in the control of heart rate. His work on K+ channels has identified the critical domains that allow appropriate assembly of channels. It explains the physiological and pharmacological properties of inwardly rectifying K+ channels in particular ATP-sensitive K+ channels. In his early career, he developed a model for how calcium passes through Ca2+-release channels to initiate cardiac contraction. This has become the dominant paradigm in the field. Finally, his work has direct clinical relevance in that it helps explains the mechanisms of certain inherited “channelopathies”. In particular, those associated with hereditary long QT syndromes and persistent hyperinsulinaemic hypoglycaemia. He is also a practising clinician and I believe he is eminently worthy of Fellowship.