Faculty
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Research Interests “Life at the Edge” In the wake of “oms and omics” lurks the realization that even simple cellular processes involve the interplay between multiple multi-subunit macromolecular complexes. How these complexes function at the molecular level, how their spatial and temporal interaction patterns are regulated, and how specificity is achieved at any given moment remains a mystery, in part because low abundance, compositional and conformational heterogeneity of macromolecular assemblies cause seemingly insurmountable obstacles for the structural exploration of life at the molecular scale. Faced by an increasing complexity at the molecular level, recent technological advances brought about a renaissance of electron microscopy, which armed with new gadgets and tools rapidly establishes itself as a key player in the battle to uncover the structural underpinnings of life. In contrast to other structural approaches, electron microscopy is extremely versatile, allowing us to explore biology from cellular to near atomic scales by analyzing images of samples that have been preserved by rapid freezing in aqueous solutions. Exploiting the versatility of modern day microscopy, our lab is interested in understanding the mechanisms of membrane associated processes, which in the realm of structural biology remain among the most elusive, and most difficult to tackle. Exploring “life at the edge” – our work is focused on problems ranging from the transport of simple ions such as copper, to understanding how cells change the shape of their membranes, and the molecular basis of synaptic scaffolding. Extending the range of our work, we also pursue biochemical, biophysical and cell biological studies to put our structural data into perspective, and to obtain a fully integrated mechanistic understanding of the processes we study. Looking to the future: BMBCB and Northwestern provide a unique opportunity to tackle another exciting challenge - the development of new tools for the high-throughput structure determination of macromolecular complexes. Specifically, we would like to develop “lab-on-a-grid” technologies that will allow us to rapidly capture macromolecular assemblies from crude cell lysates, and to preserve them for EM structural analysis within minutes of opening the cells. Combined with the development of validation methods, these efforts have the potential to “turn the tables” by putting us in a position where not structures but our ability/capacity to analyze and interpret them will be the most limiting factor towards understanding the molecular basis of life.
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Selected Publications De Feo, C.J., Aller, S.G., Siluvai, G., Blackburn, N., and Unger, V.M. (2009) “Three-dimensional Structure of the Human Copper Transporter hCTR1”, Proc Natl Acad Sci USA 106:4237-42; PMC2647337 Frost, A., Unger, V.M., and De Camilli, P. (2009) “The BAR Domain Superfamily: Membrane-Molding Macromolecules: Cell 137(2):191-196 Frost, A., Perera, R., Roux, A., Destaining, O., Spasov, K., Egelman, E., De Camilli, P. and Unger, V.M. (2008). Structural Basis of Membrane Invagination by F-BAR Domains, Cell 132(5):807-17; PMC2384079 Eng, E.T., Jalilian A.R., Spasov, K., and Unger, VM (2008). Characterization of a Novel Prokaryotic GDP Dissociation Inhibitor Domain from the G Protein-Coupled Membrane Protein FeoB. J Mol Biolg 375(4):1086-97; PMC2266681 Aller, S.G., and Unger, V.M. (2006). Projection Structure of the Human Copper Transporter at 6Å Reveals a Compact Trimer with a Novel Channel-Like Architecture, Proc Natl Acad Sci USA 103:3627-32, PMC1450133 View all publications by Vinzenz Unger listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue |