This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: After earning bachelor's and Ph.D. degrees in bioengineering with a focus on molecular biology, Will White, a postdoctoral scholar in the Department of Computer Science at Tufts, was pretty certain his future research would involve things like DNA and proteins. What he didn't know was that alpacas would also be part of the equation.
For the past two years, White has worked with the furry mammals known not only for their teddy bear–like fleece, but also for the special antibodies they produce called nanobodies. The work culminated with a new paper in the journal Communications Biology called "Functional mapping of immune nanobody repertoires with NanoMAP." The paper stems from a research project started in 2022 by Charles Shoemaker, a professor in the Department of Infectious Disease and Global Health at Cummings School of Veterinary Medicine at Tufts. For decades, Shoemaker had been working with antibodies, the proteins produced to fight off viruses and disease, and specifically with nanobodies, the mini version of antibodies that sharks and members of the camelid family—including alpacas—uniquely produce.
Like other researchers, Shoemaker was interested in the way that nanobodies, which are 10x smaller than standard antibodies, easily slip into tight spaces and reach invaders. They are also easier to work with; standard antibodies are made of four protein chains (two heavy, two light) and matching them can be difficult. Nanobodies are made only of heavy chain proteins, eliminating the need for pairing.
What Shoemaker wanted with this new project, White says, was to find a way to modernize his strategy for discovering new nanobodies. "Chuck and a lot of other people working with nanobodies tended to use more traditional methods for discovery," White says. Researchers would pick random samples from a large group, test their properties in labs, and hope they had good candidates to use in experiments—a process that is time-consuming, may miss stronger candidates to study, and often needs repeating.
Shoemaker and his team at Cummings School decided to partner with Lenore Cowen, a professor in the Department of Computer Science at the School of Engineering, and research assistant Edward Moseley, EG24, to create Nanobody Meta-clustering Analysis Platform (NanoMAP), a custom computational tool that makes it easier and more efficient for researchers to identify nanobodies that strongly bind to antigen targets. White joined the project two years ago. The process starts with alpacas rented from a local farm, White says.
Following National Institutes of Health guidelines, the alpacas are injected with a small amount of protein antigens from a pathogen—in this case from COVID-19, botulinum neurotoxin, or a parasitic blood fluke. This triggers their immune systems to produce nanobodies and fight back. Researchers collect blood samples, separate B cells (the immune cells that produce nanobodies), extract the nanobody DNA, and then reformat it into an easier-to-handle format to test its ability to bind to the antigen target and to all known variants of the antigen.
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