Research Areas, Methods, and Resources
Research Areas
Many hormones, neurotransmitters, and secretory proteins are released from cells by exocytosis, which involves complex vesicle trafficking and membrane fusion steps. Investigators at UVa are studying exocytosis and membrane fusion at the cellular and molecular level. Defects in neurotransmitter release lead to multiple neurological and neuro degenerative diseases including epilepsy, Parkinson’s, Alzheimer’s, schizophrenia, and mood disorders.
Faculty Members
Herve Agaisse, David Cafiso, James Casanova, David Castle, Carl Creutz, Bimal Desai, Anne Kenworthy, Lukas Tamm
Bacterial and viral pathogens enter cells by multiple pathways. Investigators study the uptake of bacteria and viral entry into cells that often require a membrane fusion step. Others study the behaviors of proteins on the surface or within pathogens at high molecular resolution.
Faculty Members
James Casanova, Linda Columbus, Alison Criss, Ed Egelman, Andreas Gahlmann, Peter Kasson, Anne Kenworthy, Owen Pornillos, Lukas Tamm, Judith White, Mark Yeager
Investigators at UVa are studying communication between cells, such as cardiac cells, through gap junction channels. Calcium channels are important in excitable cells including neurons and muscle cells. G protein coupled receptors are the most abundant drug targets, and UVa research seeks a better structural understanding of coupling G protein activation to ligand binding. Channels in the outer membranes of gram-negative bacteria are responsible for nutrient and antibiotic uptake and therefore important drug targets.
Faculty Members
Paula Barrett, Douglas Bayliss, Bimal Desai, Brant Isakson, Swapnil Sankusare, Lukas Tamm, Mark Yeager
Laboratories at UVa study mechanisms of active transport across membranes. Transporters that are responsible for the uptake and export of sugars, peptides, polysaccharides, vitamins, and drugs are examined structurally and functionally. Questions such as how ATP is generated by dissipating a proton gradient across membranes are being answered.
Faculty Members
David Cafiso, Robert Nakamoto, Michael Wiener, Mark Yeager, Jochen Zimmer
How do cells respond to adenosine binding to its receptor? How is calcium influx at the synapse coupled to neurotransmitter release? Are specialized lipids or platforms of proteins and lipids important in these biological circuits? UVa researchers are using multiple techniques to explore these questions that are central to human health.
Faculty Members
Paula Barrett, Douglas Bayliss, John Bushweller, David Cafiso, David Castle, Linda Columbus, Carl Creutz, Douglas DeSimone, Brant Isakson, Anne Kenworthy, Kevin Lynch, Swapnil Sonkusare, Avril Somlyo, Lukas Tamm, Mark Yeager
Methods and Resources
The UVa Molecular Electron Microscopy Core laboratory enables cryoEM and tomography for high-resolution imaging and three-dimensional reconstruction. A state-of-the-art Titan Krios has been installed in 2012 and has been equipped with a Falcon II direct detector in 2014. FEI Spirit and F20 electron microscopes are also part of the core.
Core Director: Kelly Dryden
The biomolecular nuclear magnetic resonance facility at UVa is home to one 800, three 600, and two 500 MHz spectrometers, which are equipped with triple-resonance cryoprobes. A 500 MHz solid-state NMR spectrometer with a heteronuclear MAS-probe is available for solids experiments.
More: https://med.virginia.edu/biomolecular-magnetic-resonance-facility/
Core Director: Jeff Ellena
EPR equipment includes two X-band cw spectrometers, a pulse X-band machine capable for DEER, and a pulse Q band spectrometer.
Robotics to prepare Lipic Cubic Phase, detergent or even bicelle based membrane protein crystallization is available. These instruments can set up batch or vapor diffusion experiments and the protein crystals can be visualized and docmented using polarized visible light or UV fluorescence microscopes at 4 and 17 degrees Celsius.
Research Faculty: Michael Purdy
The Center houses culture facilities for large-scale expression in bacterial, yeast, and insect cell systems. Protein purifications and characterizations are handled by individual labs and collaboratively as needed.
Research Faculty: Mark Daniels, Binyong Liang
The center houses an advanced server room; center faculty participate in the Folding@Home network, the XSEDE supercomputing grid, and several European supercomputing initiatives.
Research Faculty: Peter Kasson
Confocal, TIRF, lifetime, and laser microscopes for cell biological research and single molecule detection are available to Center researchers.
Research Faculty: Volker Kiessling
For University and School of Medicine-wide Cores, see:
W. M. Keck Center for Cellular Imaging
Director: Ammasi Periassamy
Director: Stacey Criswell
Small angle x-ray scattering (SAXS) is used to determine sizes and shapes of macromolecules and macromolecular assemblies such as protein-detergent complexes. It can be used in sample preparation to characterize the properties of samples before they are used for other purposes. SAXS is also very beneficial in combination with spectroscopy, especially NMR spectroscopy, to refine and constrain NMR structures to molecular shapes that are consistent with the SAXS data.
Faculty: Linda Columbus, Michael Wiener
The Center houses a state-of-the-art in-house x-ray generator/diffractometer/detector system and crystallization robots, and synchrotron beam time is available at the Argonne National Lab Advanced Photon Source. UVa researchers also develop new methods and media for membrane protein crystallography.
Research Faculty: Michael Purdy