Vinzenz Unger


PhD, University of Cambridge

Chemistry
Interdisciplinary Biological Sciences Program
Medical Scientist Training Program

Office Phone: 847.491.7850
Email
The Unger Lab

Research

In the wake of “oms” and “omics”, understanding of the mechanisms that govern the integrated interplay of cellular components at all levels is rapidly falling behind factual knowledge about macromolecular inventory and global interaction networks between macromolecular assemblies. One area where the divide between “knowing” and “understanding” is particularly pronounced is the biology of interfaces between cellular membranes and the compartments they enclose. This is because the chemical and physical complexity of membrane interfaces makes visualization of these compartments through direct structural methods exceptionally challenging and precludes the generation of the structural insights that inform functional, cellular and translational studies. Addressing the ensuing disconnect between colorful “bubble diagrams” and the realities of life at the molecular level, our work seeks to accelerate mechanistic understanding of the biology at membrane interfaces.

Currently, our studies are in two areas: one line of projects tries to understand the molecular mechanisms of cellular acquisition and distribution of copper ions, while other projects are focused on unraveling how cells utilize membrane-associated scaffolds to sense, stabilize, and change membrane curvature in cellular processes that range from cell motility, to cell division, intracellular cargo movements, organelle homeostasis, and biological signaling. Ultimately our goal is to understand, in molecular and atomistic detail, how exactly membrane remodeling and copper uptake/distribution work. To accomplish this goal, we draw on structural biology, computational biology, biochemistry, genetics and in vivo imaging. What sets us apart from most others is that we include membranes into our analysis (whenever possible), and that we increasingly focus our efforts on working with full-length proteins rather than using heavily truncated pieces of complex molecules. Both aspects create significant challenges for traditional approaches to structure, and single out cutting-edge electron microscopy as principal approach towards visualizing membrane proteins and membrane-associated scaffolds in the context of their natural environment – the membrane. Doing so invariably results in unexpected discoveries. That said, generation of structures is only the first step and serves to inspire functional studies that test the significance of mechanistic models both in vitro and in vivo. Because of the high degree of interdisciplinary integration, trainees in the lab are expected to acquire a broad set of skills that will allow them to take mechanistic questions from gene to cells and cellular regulation.

 

Selected Publications

Copper Uptake and Distribution

  1. 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
  2. Flores, A.G., and Unger, V.M. (2013). Atox1 Contains Positive Residues that Mediate Membrane Association and Aid Subsequent Copper Loading. J Membr Biol 246(12):903-913; PMC3827972
  3. Pope, C.R., De Feo, C.J., and Unger, V.M. (2013). Cellular Distribution of Copper to Superoxide Dismutase Involves Scaffolding by Membranes. Proc Natl Acad Sci USA 110(51):20491-20496; PMC3870662

Membrane Remodeling

  1. 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
  2. Mim, C., Cui, H., Grawonski-Salerno, J., Frost, A., Lyman, E., Voth, G.A., and Unger, V.M. (2012) “Structural Basis of Membrane Bending by The N-BAR Protein Endophilin”, Cell 149(1):137-145; PMC3319357
  3. Cui, H., Mim, C., Vazquez, F.X., Lyman, E., Unger, V.M., and Voth, G.A. (2013) “Understanding the Role of Amphipathic Helices in N-BAR Domain Driven Membrane Remodeling”, Biophys J. 104(2): 404-411; PMC3552260

 

Links

View all publications by Vinzenz Unger listed in the National Library of Medicine (PubMed).

Recent Photos

October 27, 2015