2003 Prize Winner Dr. Michael Ehlers Assistant Professor of Neurobiology and Director of the Neuroproteomics Laboratory at Duke University in North Carolina, USA
Dr. Michael Ehlers grew up in Grand Island, Nebraska, and earned his bachelor's degree in chemistry from the California Institute of Technology in 1991. He holds MD and PhD degrees since 1998 from the Johns Hopkins University School of Medicine in Maryland, where he also conducted postdoctoral research. Currently Dr. Ehlers is an Assistant Professor of Neurobiology and the Director of the Neuroproteomics Laboratory at Duke University in North Carolina. He is the recipient of numerous awards in neuroscience and a Scholar of the Ruth K. Broad Foundation. His research focuses on the interface between neuronal cell biology and the plasticity of neural circuits, with emphasis on protein trafficking and turnover mechanisms in dendrites.
For Dr. Ehler‘s full essay, see Science Online at sciencemag.org
Ubiquitin and the deconstruction of synapses.
The remodeling of synapses is a fundamental mechanism for information storage and processing in the brain. Much of this remodeling occurs at the postsynaptic density (PSD) a specialized biochemical apparatus, containing neurotransmitter receptors and associated scaffolding proteins, that organizes signal transduction pathways at the postsynaptic membrane (Figure).Far from being an immutable structure, the PSD undergoes long-lasting global changes in ist molecular composition, which are dictated by neuronal activity. These changes are bidirectional, reversible, and involve networks of PSD proteins that rise and fall in abundance as coordinated ensembles.Activity-dependent remodeling of the PSD is accompanied by altered protein turnover, which is remarkably rapid and robust. In turn, this remodeling occurs with corresponding increases or decreases in ubiquitin conjugation of synaptic proteins and requires proteasome-mediated degradation. Functionally, these modifications alter synaptic signaling to major downstream effectors.Thus, richly dynamic in its internal life, the postsynaptic density contains hidden dimensions of interconnected protein networks within which reside the molecular trace of experience. By demonstrating that activity controls the global composition of the synapse through ubiquitin-dependent turnover, our research provides a new conceptual framework for understanding and ultimately predicting functional changes in neural circuits.
Find out more about Dr. Ehlers and his work at ehlerslab.org
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