The Eliezer lab studies the role of protein disorder and dynamics in normal neuronal function and in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, with a focus on protein-membrane interactions and protein aggregation.
The Eliezer lab studies the structural properties and interactions of disordered proteins (IDPs) and protein regions that are involved in the communication between neurons, with a focus on the synaptic vesicle cycle at presynaptic nerve terminals. To contend with inherent challenges in the structural characterization of IDPs, the lab typically employs spectroscopic methods including nuclear magnetic resonance (NMR) spectroscopy as well as as optical spectroscopic methods. Because many of the proteins that we study interact with biological membranes such as synaptic vesicles, the plasma membrane or mitochondria, our work also includes aspects of membrane biophysics. A major project in the lab involves studies of the membrane interactions of the Parkinson’s protein alpha-synuclein, which interacts with synaptic vesicles and contributes to the regulation of vesicle release. The aggregation of alpha-synuclein into amyloid fibrils is also a subject of study in the lab. The protein tau, which forms amyloid fibrils in Alzheimer’s disease, comprises another major topic of research in the lab. In neurons, tau is largely bound to microtubules, which form the basis for the shuttling of proteins and other cellular components to and from nerve terminals located far from cell bodies. Besides binding to microtubules, tau interacts with other cellular components and its interactions with membranes is of particular interest to the lab, as these result in the formation of unique oligomeric tau species that may be important in disease. In addition to spectroscopic methods, we are also employing recent advances in cryo-electron microscopy to elucidate the structure of disease-associated amyloid aggregates.
Where possible, we complement our structural studies with functional assays performed in vitro, in living cells or in intact organisms, often in collaboration with other groups. We have elucidated functional interactions of alpha-synuclein with small GTP-hydrolyzing Rab proteins and characterized the effects of this interaction on enzymatic activity. We have explored the effects of wild-type and mutant alpha-synuclein on vesicle release and mitochondrial function/dysfunction in living cells, combining these assays with our structural work to implement structure-function analyses. We have also investigated the role of the intrinsically disordered C-terminal tail of the protein complexin in regulating SNARE-mediated synaptic vesicle release in living worms, again combining these studies with structural investigations to highlight the role of complexin-membrane interactions in its function.
Biography
David Eliezer obtained his Ph.D. from Stanford University where he studied the process of protein folding under the guidance of Seb Doniach, Keith Hodgson and Buzz Baldwin. He performed post-doctoral work at the Scripps Research Institute working under Peter Wright to apply nuclear magnetic resonances (NMR) spectroscopy to the characterization of partly ordered protein folding intermediates. He joined the faculty at Weill Cornell in 1999, where he is currently a tenured Professor of Biochemistry.
