About our Research

The Ward lab is using the broad resolving power of the electron microscope (EM) and cutting edge biophysical techniques to investigate the intersection between viral pathogens and the immune system.

We are using all of these techniques in order to identify and characterize vulnerable sites on viral proteins and the structural constraints that are shaping the immune system’s response to invaders such as HIV-1, Ebola, and Influenza. This approach will allow us to correlate molecular level details with immunogenicity results, thereby enabling rational vaccine and drug design efforts.

We take full advantage of the Molecular Microscopy Suite at The Scripps Research Institute featuring the powerful Titan Krios and Talos microscopes for high-resolution Cryo-EM studies, as well as several other microscopes paired with direct electron detectors that produce high-quality images for our studies. Our structural studies are complemented with a suite of advanced biochemistry and biophysical techniques, such as Bio-Layer Interferometry, Differential Scanning Calorimetry, and Multi-Angle Light Scattering (MALS).
Rational Vaccine Design: Understanding the Molecular Mechanisms of Antibody-Mediated Protection
Broadly neutralizing antibodies targeting these surface spikes have been shown to provide protection against viruses such as HIV and Influenza. We are trying to better understand how these antibodies bind to and neutralize viruses in order to design vaccines that will ellicit these highly protective antibodies. Using single particle electron microscopy and electron tomography, we are able to visualize the interactions between the antibodies and the viral proteins, providing detailed information about the mechanism of inhibition necessary for improving the design of better immunogens for eliciting a broadly neutralizing antibody response in humans.
Antibody-Mediated Therapeutics: Characterizing Sites of Virus Vulnerability
Therapeutic antibody cocktails have shown efficacy against and show significant promise for eventual human use, most recently against the lethal Ebola virus. Using electron microscopy, we aim to provide a detailed roadmap to both effectively screen through hundreds of candidate antibodies to find the optimal immunotherapeutic cocktail combination. Additionally, using BioLayer Interferometry in particular, we aim to determine the mechanism of protection to better assess antibody based therapeutics, like Zmapp.
Applied Biophysics: Developing New Therapeutics and Pursuing Novel Structural Targets
We are also interested in using x-ray crystallography, electron microscopy, and other biophysical techniques to study novel membrane proteins such as:
  • Membrane protein transporters that mediate the passage of a wide variety of molecules into and out of the cell. The molecular details underlying the function of most transporters are still unknown.
  • Membrane-bound cell surface receptors that are recognized and exploited by viruses to mediate viral entry into the cell via endocytosis or membrane fusion. This work complements our other projects targeting the viral proteins and presents another opportunity for advancing novel therapeutics preventing viral diseases.