Directed Evolution of Nanobodies for COVID-19 Prevention
Department of Biological Sciences
North Carolina State University
Directed evolution is a laboratory process that mimics the steps of natural selection to efficiently determine variants of proteins or organisms that respond more effectively to a selected condition. This process was recognized by the 2018 Nobel Prize in Chemistry awarded to Dr. Frances Arnold and has widespread applications, ranging from industrial enzymes to food-producing yeast. Recently, this technology has been applied to identifying and improving potential therapeutics to protect against infection by SARS-CoV-2, the virus that causes COVID-19. In this jigsaw case study, students become experts on the various components of such research (including directed evolution, yeast surface display, nanobodies, and protein binding) before teaching their peers and applying their newly acquired knowledge to the interpretation of a primary research article on SARS-CoV-2. As a concluding activity, students create a concept map or diagram connecting the directed evolution process to natural selection. The case includes two levels of sophistication, which are clearly indicated: introductory (Level 1) and advanced (Level 2). The case was developed for use in either an introductory biology or genetics course (Level 1) or an upper-level molecular biology course (Level 2).
- Describe nanobodies and how they differ from antibodies.
- Articulate the features and purpose of a yeast surface display library.
- Diagram the process of directed evolution of proteins.
- Compare and contrast directed evolution with natural selection.
- Explain how nanobodies can block transmission of SARS-CoV-2.
KeywordsDirected evolution; natural selection; high-throughput; antibodies; COVID 19; Spike; spike protein; nanobodies; affinity; protein binding; yeast surface display; library; SARS-CoV-2; protein engineering
Educational LevelUndergraduate lower division, Undergraduate upper division, Graduate
Type / MethodsDirected, Flipped, Jig-Saw
Subject HeadingsBiochemistry | Biology (General) | Biotechnology | Evolutionary Biology | Molecular Biology |
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The following video(s) are recommended for use in association with this case study.
- Polymerase Chain Reaction (PCR)
Animation of the process of PCR at the molecular level. Running time: 1:27 min. Produced by DNA Learning Center, 2010.
- Yeast Surface Display
Slide show presentation of the principles of antibodies, their variety, and their display on the surface of yeast for the purpose of screening. Running time: 3:25 min. Produced by Andrea Bixler, 2021.
- Mini-Antibodies Discovered in Sharks and Camels Could Lead to Drugs for Cancer and Other Diseases
Animated video explaining the origin and uses of nanobodies. Running time: 2:37 min. Produced by Science Magazine, 2018.
- Flow Cytometry Animation
Animation showing the inner workings of a flow cytometer. Running time: 4:35 min. Produced by StarCellBio, 2015.
- Frances Arnold | Directed Evolution of Enzymes | 2014 National Inventors Hall of Fame Inductee
Dr. Frances Arnold discusses how she developed the process of directed evolution to engineer proteins. Running time: 2:10 min. Produced by National Inventors Hall of Fame, 2014.