As part of a new series of posts from CVR staff and students about their work, CVR postdoc Chris Syme, writes about his research in the Bhella lab on the structural biology of viruses like Zika virus using a diverse array of imaging techniques. If you would like to hear more about one of the techniques Chris writes about then check out our podcast episode with Swetha, another postdoc in the Bhella lab. Contagious Thinking serves to communicate the science of the CVR and provide important training and exposure opportunities for our staff and students like this. If you would like to write a short article about your research, please contact a member of the communications team.
My work at the CVR is focused on the Zika virus and how it may be neutralized by antibodies. I work in David Bhella’s group who use cryogenic electron microscopy (or cryo-EM) to study the structure of viruses and virus-like particles (VLPs), as well as the interaction of viruses with various ligands such as receptors, antibodies and others proteins. Cryo-EM is an imaging technique that has recently advanced to the point of being able to generate near-atomic resolution structures comparable to those obtained by X-ray crystallography, but has the advantage of not requiring the sample to be crystallized. Thus cryo-EM can be used to study biological molecules such as proteins and whole viruses in their native state, including virus particles within cells.
To obtain near-atomic resolution structures from cryo-EM, it is necessary to take a large number of images that contain individual virus particles at various orientations. These images are then processed en masse to generate a complete three-dimensional structure of the sample, reconstructed from the information contained within the original images. For cryo-EM measurements, samples need to be purified and highly concentrated. Much of my day-to-day work is centered on optimizing the conditions for the growth and purification of highly concentrated virus samples, as well as learning how to conduct cryo-EM measurements and how to process the resulting images.
I came to the CVR in July 2016 after having worked in a number of different research areas, including biochemistry, engineering and chemistry. After obtaining a PhD in Chemistry from the University of Glasgow, I moved to London (QMUL/NIMR/UCL) for my first postdoc which involved structural studies of a peptide implicated in Alzheimer’s Disease (amyloid beta, Ab) and its complexes with metal ions. I subsequently moved back to Glasgow to work in the School of Engineering on the development of lab-on-a-chip devices for live cell imaging. Since then, I have worked at the School of Chemistry studying crystal nucleation processes via a range of spectroscopic and imaging techniques, as well as preparing a fellowship application.
With a view to gaining expertise relevant to my fellowship application, I obtained a grant from the Scottish Funding Council in 2015 which enabled me to work as a visiting researcher at University of California Irvine, where I helped to build a new type of ultra-sensitive microscope based on CARS (coherent anti-Stokes Raman), the results of which were published in 2016. I intend to submit my fellowship application in 2017, but in the meantime, I am working at the CVR and learning how to produce high-quality virus samples for cryo-EM imaging. My work at the CVR will complement my fellowship application since viruses and VLPs are a key target for the kind of research that I am proposing to do, while also gaining practical experience in cryo-EM, which promises to be an invaluable tool for biological structural studies in the future.
Thank you to Chris for contributing as part of a short series of articles on Contagious Thinking. Look out for more articles from new contributors in the very near future. If you would like to write a short article about your research, please contact a member of the communications team.