Nanobody Discovery Hub
Lead Research Organisation:
Rosalind Franklin Institute
Department Name: Research
Abstract
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.
Technical Summary
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.
Organisations
Publications
Hricovíni M
(2022)
Chemistry towards Biology-Instruct: Snapshot.
in International journal of molecular sciences
Eyssen L
(2024)
From Llama to Nanobody: A Streamlined Workflow for the Generation of Functionalised
in Bio-Protocol
Mycroft-West CJ
(2024)
Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1.
in Nature communications
Gao X
(2023)
The solution structure of the heavy chain-only C5-Fc nanobody reveals exposed variable regions that are optimal for COVID-19 antigen interactions
in Journal of Biological Chemistry
Description | Nanobodies are recombinant antigen-specific single domain antibodies (VHHs) 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 numerous applications in the biomedical sciences. We have developed a standardised workflow and data management system, AntigenApp, for nanobody discovery, prioritisation, and production. We have applied this workflow to the generation of nanobodies to different antigens from both immunised and naïve or non-immunised VHH libraries. |
Exploitation Route | A collaborative access model will be developed to make the technology available to the UK Biosciences community and the technology has already been disseminated through a worhskop (October 2022) and is publicised on the Rosalind Franklin Institute website (https://www.rfi.ac.uk/projects/nanobody-discovery/) |
Sectors | Healthcare |
URL | https://bio-protocol.org/e4962 |
Description | Engineering of nature-mimetic sub-micron crystalline protein depots to incorporate high cargo densities |
Amount | £214,923 (GBP) |
Funding ID | 10086682 |
Organisation | Innovate UK |
Sector | Public |
Country | United Kingdom |
Start | 02/2024 |
End | 01/2025 |
Description | Interview (Royal Institution Christmas lecture) |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Interviewed on COVID 19 and nanobodies part of the 2021 Royal Institution Christmas Lecture "Going viral- Part 3: fighting back" |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.bbc.co.uk/iplayer/episode/m0012tzh/royal-institution-christmas-lectures-2021-3-fighting-... |
Description | Public exhibition |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Llamas vs viruses was one of the 16 exhibits at the 2022 Royal Society summer science exhibition attended by a wide cross-section of the public including schools groups and informed about our work on llama derived antibodies for the potential treatment of viral diseases such as COIVD 19. |
Year(s) Of Engagement Activity | 2022 |
URL | https://royalsociety.org/science-events-and-lectures/2022/summer-science-exhibition/all-exhibits/ |