Camelids (think llamas, alpacas and of course, camels) produce rather special antibodies that are highly sought after for research and biomedical applications. Nanobodies are small fragments of camelid antibodies that retain the ability to identify specific proteins. Because they are so small, they can bind to segments of proteins that intact or larger antibodies are unable to contact. This is what makes them attractive candidates in the search for new disease-fighting drugs. Obtaining these nanobodies is not easy though as it requires immunizing animals using specific proteins and waiting for antibodies to be produced against those proteins.
A team of researchers have now developed a way to create these special antibodies using yeast. They used DNA sequences from camelid nanobody genes to develop a library containing millions of nanobodies attached to individual yeast cells. To find nanobodies that can bind to specific proteins, they expose the yeast cells to proteins labelled with a fluorescent tag and then determine which cells the proteins adhered to.
McMahon C, Baier AS, Pascolutti R, Wegrecki M, Zheng S, Ong JX, Erlandson SC, Hilger D, Rasmussen GF, Ring AM, Manglik A, Kruse AC. Yeast surface display platform for rapid discovery of conformationally selective nanobodies. Structural & Molecular Biology. 25: 289–296, 2018.
Harmsen MM, De Haard HJ. Properties, production, and applications of camelid single-domain antibody fragments. Applied Microbiology and Biotechnology. 77(1): 13-22, 2007.