Nanobody Discovery Hub

The genomics revolution has opened up the protein world for discovery research in medicine, biosciences and biotechnology. Interpreting and exploiting this information necessitates an understanding of how proteins function as part of complex and dynamic macro-molecular assemblies in cells. Single domain antibodies or nanobodies are powerful tools for tagging and tracking proteins and their interactions. They can lock proteins into specific shapes that makes it easier to study their structure. By making nanobody technology more widely available to the UK Biosciences research community, the Nanobody Discovery Hub project will help accelerate research into how proteins work and how this knowledge can be usefully applied in structural, cell and synthetic biology.

Nanobodies are recombinant antigen-specific single domain antibodies derived from the heavy chain only subset of camelid immunoglobulins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with multiple applications in the biomedical sciences, including super-resolution microscopy and non-invasive imaging. In structural biology, the use of nanobodies has been transformative enabling the analysis of complex macromolecules including integral membrane proteins. Co-crystallization with nanobodies that recognise and stabilise specific functional/conformational states, has enabled the structural analysis of a membrane proteins in particular G-Protein Coupled Receptors. Similarly nanobodies are facilitating structure determination by cryo-Electron Microscopy (cryoEM) by locking proteins into specific conformations. In a three year project, the Nanobody Discovery Hub will develop and make available the generation and engineering of nanobodies to the UK Biosciences research community by establishing an access programme controlled by independent peer-review. In addition a workshop and two practical training courses will be organized to disseminate the technology. The workflow for generating nanobodies by screening both immunised and naive llama libraries has been prototyped and shown to be readily scaleable. Informatic tools will developed for managing and annotating the nanobody sequences generated by the project so that these data can subsequently be mined to aid in the design of novel or improved binders.