Biomimetic Surfaces for Probing Virus-cell Interactions..
Mon, Sep 09
2:00 PM — 3:15 PM
Steinman HallSteinman Hall 160 - Lecture Hall
Steinman Hall, 160 - Lecture Hall
The ChE Department would like to welcome Professor Susan Daniel from Cornell UniversityClass I membrane-enveloped viruses, such as influenza and coronavirus, infect host cells through the endocytotic pathway. For this class of viruses, one essential viral coat protein is responsible for both the attachment of the virus to the host cell (binding) and the fusion of the viral membrane with the host membrane. Because one protein controls both processes, it is challenging to obtain entry kinetics with traditional ensemble assays. To differentiate these processes, we use single virion imaging techniques to quantify virus-host interactions in a biomimetic system that captures many features of the natural infection process. In nature, these viruses bind to receptors present on the surface of cells. This event initiates viral uptake into an endosome. Once inside the endosome, the viral membrane must fuse the endosomal membrane in order to delivery its genetic material to the cytosol for replication. Viral fusion to the endosomal membrane is initiated by a conformational change in the viral fusion protein, triggered by acidification of the endosome, among other stimuli. Different strains and serotypes of virus can have markedly different binding and fusion characteristics. Characterizing this behavior is important for basic biological studies of virus entry that assist in identifying new anti-viral drugs that target viral entry processes, creating new diagnostic tools for differentiating virus types, and developing new biosensors. The development of such platforms requires an appropriate mimic for the host cell surface that presents the receptors for viral interaction, and a strategy to acidify the system to mimic the pH drop inside the endosomal compartment to initiate membrane fusion. We developed an in vitro platform for assaying binding and fusion of single virion particles using an individual virion imaging technique and analysis of stochastic data. In this work, we mimic the host membrane chemistry in a supported bilayer coating the walls of a microfluidic device. The physico-chemical properties of the bilayer can be controlled to present different receptors and surface features that may modify virus-host interactions. Most recently, we developed a method to create supported bilayers from cell plasma membranes, allowing us to expand this technique to viruses that rely on proteinaceous receptors for entry. I will present recent results on entry kinetics of coronavirus, a class I virus responsible for SARS-CoV outbreak in 2002 and the emerging MERS-CoV strain causing the outbreak of 2013.
Professor Susan Daniel is an assistant professor of chemical and biomolecular engineering at Cornell University. She obtained her B.S., M.S., and Ph.D. (2005) from Lehigh University in chemical engineering. In her graduate work, she pioneered systems to manage digital droplet fluidics by engineering interfacial surface chemistry and drop shape fluctuation to actuate droplet motion. Following her graduate work with Manoj Chaudhury, Professor Daniel joined Paul Cremer’s research group in chemistry at Texas A&M University. There she applied her knowledge of interfacial chemistry to biological membranes and developed novel biosensing and biomimetic membrane assays. She was a post doctoral associate in the Cremer lab for 2.5 years until she began her independent laboratory at Cornell in 2007.
The common theme of Professor Daniel’s research at Cornell is investigating how the organization of molecules at a surface impacts the interactions of the interface with other materials. In particular, her group is interested in the dynamic phenomena that result from those interactions. Her groups studies phenomena at both biological interfaces and chemically patterned surfaces that interact with soft matter – liquids; polymers; and biological materials, like cells, viruses, proteins, and lipids. Her group has pioneered development of single particle tracking assays to study pathogen-host interactions, and the development of virus-like proteoliposomes and supported planar bilayers that facilitate those studies.
Professor Daniel is the recipient of a National Science Foundation CAREER award in 2011 and the Denice Denton Emerging Leader Award in 2012. She is also the faculty advisor for the Chemical and Biomolecular Engineering graduate women’s group (CBE Women), which serves to provide professional development and leadership opportunities to graduate students to complement their graduate education.