“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: Molecular Biosciences 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.
Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers. Opatowsky Y, Lax I, Tomé F, Bleichert F, Unger VM, and Schlessinger J. PNAS. 2014 February 4;111(5):1772-1777.
Cellular distribution of copper to superoxide dismutase involves scaffolding by membranes. Pope CR, De Feo CJ, and Unger VM. PNAS. 2013 December 17;110(51):20491-20496.
Atox1 Contains Positive Residues that Mediate Membrane Association and Aid Subsequent Copper Loading. Flores AG and Unger VM. Journal of Membrane Biology. 2013 December;246(12):903-913.
Protein-Mediated Transformation of Lipid Vesicles into Tubular Networks. Simunovic M, Mim C, Marlovits TC, Resch G, Unger VM, and Voth GA. Biophysical Journal. 2013 August 6;105(3):711-719.
Autoinhibition of Endophilin in Solution via Interdomain Interactions. Vásquez FX, Unger VM, and Voth GA. Biophysical Journal. 2013 January 22;104(2):396-403.
Understanding the Role of Amphipathic Helices in N-BAR Domain Driven Membrane Remodeling. Cui H, Mim C, Vásquez FX, Lyman E, Unger VM, and Voth GA. Biophysical Journal. 2013 January 22;104(2):404-411.
Evaluation of Electron Crystallographic Data from Images of Two-Dimensional Crystals. Unger VM. Methods in Molecular Biology. 2013;955:211-227.
Electron crystallography — the waking beauty of structural biology. Pope CR and Unger VM. Current Opinion in Structural Biology. 2012 August;22(4):514-519.
Structural Basis of Membrane Bending by the N-BAR Protein Endophilin. Mim C, Cui H, Gawronski-Salerno JA, Frost A, Lyman E, Voth GA, and Unger VM. Cell. 2012 March 30;149(1):137-145.
Structure and Function of Copper Uptake Transporters. Pope CR, Flores AG, Kaplan JH, and Unger VM. Current Topics in Membranes. 2012;69:97-112.
Two modes of interaction between the membrane-embedded TARP stargazin’s C-terminal domain and the bilayer visualized by electron crystallography. Roberts MF, Taylor DW, and Unger VM. Journal of Structural Biology. 2011 June;174(3):542-551.
View all publications by Vinzenz Unger listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.