July 30, 2020
James Carothers and Jesse Zalatan
James Carothers , Dan Evans Career Development Associate Professor of Chemical Engineering, and Jesse Zalatan , Assistant Professor of Chemistry, have been awarded a National Science Foundation EAGER grant to develop a new type of SARS-Cov-2 antibody test. Reliable and widely-available SARS-CoV-2 antibody testing is critical for researchers to better understand the level of antibodies needed for protection, how long SARS-CoV-2 antibodies last, and the viral loads needed to generate antibody responses.
The team will create an inexpensive, highly-accurate platform to rapidly detect SARS-CoV-2-specific antibodies in patient samples, helping public health officials track the spread of COVID-19, respond to outbreaks and support the development of diagnostics, treatments, and vaccines.
Early Concept Grant for Exploratory Research (EAGER) awards support "high risk, high reward" exploratory research projects involving radically different approaches, the application of new expertise, or novel disciplinary or interdisciplinary perspectives. Carothers and Zalatan will receive $300,000 over a one-year period from funds made available through the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
Coronavirus antibody tests are performed to determine if a patient has previously been infected with SARS-CoV-2, the virus that causes COVID-19. Enzyme-linked immunoassays (or ELISAs) are commonly used to detect the levels of antibodies in the blood by measuring the binding of antibodies to specific viral proteins (antigens). Researchers in the Carothers and Zalatan labs will develop a scalable, low-cost alternative to ELISAs. They will create a cell-free transcription and translation (TXTL) platform that can measure SARS-CoV-2 antigen-antibody binding with the quantitative precision of an ELISA, but the easy customizability of a system that is entirely genetically-encoded.
This platform builds on previous work from the Carothers and Zalatan labs in which they created new CRISPR-Cas tools to activate gene expression (CRISPRa) in bacterial and cell-free systems. The team will now work on engineering a system where CRISPRa activity depends on the presence of coronavirus antibodies in a patient sample and is coupled to visible outputs that can be easily measured. The resulting platform could potentially be used as part of a point-of-care diagnostic in the future.
"Developing scalable approaches to rapidly quantify antigen-antibody binding is a long-standing scientific and engineering challenge," says Carothers. "While a number of CRISPR-based tools are being adapted to detect a virus' genetic material, the system we are proposing here to detect protein antibodies is really the first of its kind."
Carothers and Zalatan are both members of the Molecular Engineering & Sciences Institute (MolES) at the University of Washington. Learn more about ongoing COVID-19 research from other MolES faculty members by visiting https://www.moles.washington.edu/covid-19-research-at-moles/