A Morgridge Institute for Research project intended to shed light on planarians — remarkable flatworms capable of almost limitless regeneration — is being repurposed to focus on the novel coronavirus causing COVID-19.
Phil Newmark’s regenerative biology lab at Morgridge had originally planned in early 2020 to launch a research project using nanobodies to learn more about key proteins in their studies of planarians and schistosomes. Nanobodies are antibodies produced by camelids — llamas, alpacas, camels and others of that family — that happen to be extremely small, roughly one-tenth the size of antibodies produced by humans. Their size and simplicity make them easier to produce, and better able to penetrate densely crowded molecular environments in tissues.
“Even if it’s not appropriate for diagnosis or therapy, it’s possible that we might come across a nanobody that people could use to study the virus in their own research.”John Brubacher
Unfortunately, the timing of the COVID-19 pandemic stopped this inquiry in its tracks. But Newmark recognized that nanobodies would also be valuable tools for the study of SARS-CoV-2 (the virus causing COVID-19) with the potential to advance our fundamental understanding of the virus, and identify targets of diagnostic and therapeutic value. We agreed to green light the project and Newmark Lab visiting assistant scientist John Brubacher is leading the effort.
As a developmental biologist, Brubacher says that anything they might find of value in fighting COVID-19 would be quickly handed over to the virology experts. “I would be happy if we were just able to find a nanobody that would be useful in a research setting,” he says. “Even if it’s not appropriate for diagnosis or therapy, it’s possible that we might come across a nanobody that people could use to study the virus in their own research.”
But the clinical possibilities are also intriguing. For example, scientists are looking at whether nanobodies could be used to inhibit viral replication inside the body. “The idea is that if the antibody binds to the right place on the surface proteins of the virus, it might block the ability of the virus to enter into cells, which would really help in shutting down an infection,” Brubacher says. “And because nanobodies are so small, one could imagine using them in an inhalable medication rather than injected.”
The project is also a likely win-win for the Newmark Lab. Brubacher has not worked with nanobodies before, they’re a relatively new diagnostic tool, so the work on a coronavirus will inform the longer-term effort with flatworms. For both studies, they will be using a library of nanobody-producing yeast cells developed by a Harvard University lab, which contains millions of different variations of nanobodies — each binding to a very specific thing.
Adds Brubacher: “Essentially what I’m doing is using the coronavirus spike protein as bait to try to fish yeast cells out of that library that bind to that particular protein.”