A research team working under Professor Won Do Heo from the Department of Biological Sciences has developed a method to optically activate intracellular antibodies. Daseuli Yu is the first author of the research paper, which is currently in press for Nature Methods, a world-renowned journal which publishes papers related to new laboratory techniques.
The research team developed an optobody, an optogenetically activated intracellular antibody, which is able to regulate antibody activation. The mechanism involved the use of green fluorescent protein (GFP)-nanobodies, which are miniscule antibody fragments that can be stimulated with blue light. When stimulated, the GFP-nanobodies attach to and activate GFPs. The GFPs then inhibit key proteins involved in cell migration, which is a key component in the immune response system. The research team also compared the GFP-nanobodies to a variety of other optobodies.
In addition to optobodies, the research team developed chemobodies, which are chemically activated intracellular antibodies, and developed a technique to join two antibody fragments using the drug rapamycin. After unification, the antibody regains the ability to inhibit cell migration.
The study’s significance stems from the paradigm of antibodies as inactivated when fragmented and reactivated after recombination. The selectivity of the antibodies illustrates their potential use in biosensors, which are able to monitor the activities of specific proteins in real time. Previous methods to control antibody activity involved the use of chemical substances to repress the expression of antibodies. However, these methods do not provide precise control. Furthermore, the research on optobodies conducted by Professor Heo provides a method for the precise spatial and temporal control of antibody activity.
Professor Heo commented that “The developed technique, which provides optogenetic control of antibodies, can be utilized in research to control specific proteins with optical stimulation. I also look forward to further applications in antibody development and cancer immunotherapy.”