Oliver Clarke, PhD Receives the 2023 Irma T. Hirschl Award
Dr. Brambrink and the Department of Anesthesiology proudly congratulate Dr. Oliver Clarke, recipient of the 2023 Hirschl Charitable Trust Research Scientist Award. The award supports the work of exceptional early-career biomedical scientists at Columbia University Irving Medical Center. The trust provides faculty development and consistent funding over five years, allowing investigators to conduct novel research that contributes to new scientific knowledge and improved clinical care across disciplines.
The award will fund the Clarke lab’s research on ankyrin complexes, a topic of outstanding physiological and pathophysiological significance. Ankyrins are giant spring-like proteins that modulate cellular shape and membrane curvature in erythrocytes, neurons, and myocytes. Ankyrins also organize membrane transport proteins (eg, ion channels and others) into subcellular restricted compartments.
In erythrocytes, mutations in ankyrin complexes lead to several hereditary anemias in which the shape of the cell is dysregulated. For example, in hereditary spherocytosis (HS), erythrocytes are sphere-shaped, fragile, and rapidly cleared by the spleen. Other ankyrin mutations lead to Purkinje cell neurodegeneration, presumably due to disruption of ion channel clusters in the axon initial segment.
Dr. Clarke uses single particle cryo-electron microscopy and cryo-electron tomography (cryoEM and cryoET, respectively) to understand how ankyrins interact with other elements of the erythrocyte membrane proteome, and with the spectrin-actin cytoskeleton, in order to modulate membrane curvature. This work has important emerging implications for both physiology and disease.
The first paper from Dr. Clarke’s laboratory on this project, describing the architecture of the human erythrocyte ankyrin-1 complex, was recently published in Nature Structural & Molecular Biology, accompanied by a “News and Views” piece from a leading researcher in the field. Having solved the initial structures using cryoEM, Dr. Clarke will now study the architecture of the ankyrin complex in native erythrocyte membranes using cryoET. This will allow him to probe not just the architecture of the isolated complex, but to characterize higher-order assemblies of ankyrin complexes and their interactions with the spectrin-actin cytoskeleton. This work is likely to lead to exciting insights into the mechanism by which the ankyrin complex modulates membrane curvature, and thereby controls cellular shape.
Dr. Clarke is an Assistant Professor of Physiology (in Anesthesiology) who was originally recruited as part of a collaborative effort at Columbia by the Department of Anesthesiology, the Department of Physiology/Cellular Biophysics, and the Cardiovascular Precision Medicine Program in the Irving Institute.