Elizabeth R. Wright
Associate Professor, Department of Pediatrics
Division of Infectious Disease
ResearchThe Wright lab uses cryo-electron microscopy and molecular biology approaches to explore the three dimensional structures of bacteria, viruses, and macromolecular complexes. The goal is to use this information to aid in the development of novel antimicrobials, therapeutics, and vaccines.
The flagella and pili of many bacteria are essential for motility, adherence, biofilm formation, and are often crucial virulence factors for pathogenic species. For many species, the two appendages are temporally and spatially regulated and organized to work either in synchrony or alternately in order to coordinate motility and surface colonization. Our long-term goal is to understand 1) the structural implications of the incorporation of multiple flagellins into the flagellar filament and 2) the structural variation between pili at the macromolecular level. Currently, we use two model systems, Vibrio species and Caulobacter crescentus, to study bacterial pathogenesis and virulence, bacterial appendage structure and function, and bacteria-bacteriophage interactions.
Our long-term goal is to understand the structural basis of virus assembly in pleiomorphic viruses, using HIV, respiratory syncytial virus (RSV), and measles virus (MeV) as model systems. These projects explore how the viral proteins, cellular proteins, cellular/viral membrane composition, and cell type define the structure of the assembling and budding virus.
In addition to the biological projects, we are developing and implementing technologies and methods to push the limits of cryo-EM and its correlation with other imaging modalities.
- Zernike phase contrast TEM. We are one of the few labs in the United States to have a 200 kV FEG-TEM specifically designed and engineered for Zernike phase contrast TEM. This technology provides an advantage for achieving higher resolution and higher contrast cryo-EM/cryo-ET images of low contrast biological specimens, especially isolated macromolecules, viruses, and bacteria.
- Correlative light and electron microscopy. We are developing novel equipment and molecular biology approaches for bridging the information gap between cryo-EM and fluorescence microscopy. This includes the design, manufacture, and use of cryo-stages for confocal microscopy. By rapidly freezing cells cultured on EM grids, we are able to directly correlate fluorescence microscopy images to images collected in the electron microscope. This technology is being applied to fundamental questions about the assembly and trafficking of viruses, like HIV and RSV, within host cells.
- Affinity capture of enveloped viruses. We are developing methods for the selective capture and purification of enveloped viruses directly onto cryo-EM grids. Many enveloped viruses are extremely pleiomorphic, grow to low titers in culture, are cell-associated, and require the use of purification strategies that may alter the native structure of the virus. We have applied affinity technologies to address challenges associated with structural studies of enveloped viruses. The improvements realized by using affinity capture will be of benefit as we address basic questions regarding the structures of several families of enveloped viruses.