Eamonn, Dickson, PhD
Name of Institution:
University of California Davis, Davis, CA
α-synuclein dependent remodeling of membrane contact sites as a driver of Parkinson’s disease neurotoxicity
Eamonn Dickson is an Associate Professor at the University of California, Davis. He completed his PhD in cellular and molecular pharmacology and physiology at the University of Nevada, Reno with Dr. Terrance Smith and his post-doctoral work at the University of Washington with Dr. Bertil Hille. The long-term goals of the Dickson lab are to understand the molecular mechanisms underlying changes in ion channel function, signal transduction, and broader cellular programs of gene expression in Parkinson’s disease (PD).
To define how α-synuclein aggregation alters the structure and function of calcium channel domains at membrane contact sites – regions where internal membranes within the neuron contact each other. We aim to understand how these alterations precipitate neurodegeneration.
α-synuclein aggregation is a key pathological hallmark of PD. Despite this knowledge we lack information regarding the molecular pathways perturbed by α-synuclein that lead to cell death. The typical motor symptoms of PD can be ascribed to the progressive and selective degeneration of dopamine neurons within the substantia nigra. These neurons display oscillations in cytoplasmic calcium that are essential for dopamine synthesis and adenosine triphosphate (ATP) production. Aberrant calcium activity within these neurons is thought to be a leading cause of neuronal death in PD. A key portal for calcium entry into neurons is at membrane contact sites – regions in the cell where membranes of different internal structures contact each other and facilitate communication between cellular regions. However, it is not known how these calcium signaling domains are altered in PD and how they contribute to neurodegeneration in PD.
Using super-resolution imaging and patch-clamp electrophysiology, we will map the nanostructural and functional changes in ion channel distribution and activity at membrane contacts sites in models of PD
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
For the first time, this work will quantify the structural and functional rearrangements that occur in ion channels at membrane contact sites in dopaminergic neurons of the substantial nigra. Understanding how α-synuclein alters these crucial portals of information transfer is critical and represents an important first step in determining how PD neurodegeneration progresses at the molecular level and interferes with inter-organelle communication. By defining mechanisms through which α-synuclein alters these membrane contact sites to increase dopamine neuron vulnerability, we can selectively target these sites with the aim of slowing the progressive neurodegeneration of PD.