Paul F. Cranefield Award
Ivy E. Dick for “CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms”
Dick and colleagues show that mutations in the Cav1.2 channel in patients affected by Timothy syndrome 2 with cardiac only phenotypes affect calcium- and voltage-dependent inactivation but mutations in patients with cardiac and neurological phenotypes also affect channel activation. This is an important step to understand the pathology of Timothy syndrome and paves the way for therapeutic intervention.
Cranefield Postdoctoral Fellow Award
Krishna Reddy for “The archaeal glutamate transporter homologue GltPh shows heterogeneous substrate binding"
Reddy and colleagues show that the lyotropic properties of anions binding to GltPh, an archaeal homologue of glutamate transporters, regulate the transporter’s conformational flexibility possibly explaining why GltPh displays long-lived ‘kinetic heterogeneity’ in its transport behavior, thus providing a blueprint to understand how anions might contribute to regulating the overall transporter rate.
Cranefield Student Award
Nicole Godellas for “Probing function in ligand-gated ion channels without measuring ion transport"
In this manuscript Godellas and Grossman revisit the classical equilibrium competitive radioligand binding method to show that, once true binding equilibrium is achieved, the ligand binding sites in the α7 nicotinic acetylcholine receptor channels are identical and independent and that distal mutations have little to no effect on binding affinity and affect only the gating equilibrium constant. This approach paves the way to study ion-channel function when electrophysiological studies are not possible.
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