A study of novel nanobodies generated to cell surface biomarker proteins using phage display technology

Project background and description 

The Structural Biology Science Technology Platform (SB STP) comprises a team of experts in protein expression and purification, biophysical characterisation, and protein structure determination (X-ray, SAXS and CryoEM) using state-of-the-art equipment. The successful candidate will work on a project at the interface between structural biology and imaging in collaboration with the Electron Microscopy STP at the Crick [1].

The project involves characterising nanobodies targeting neuronal and immune cell-surface markers, selected by phage-display technology, derived from immunized llamas [2]. Characteristics of individual nanobodies such as affinity, epitope overlap, and thermal stability will be determined by BLI and NanoDSF (Prometheus). Additionally, the structure(s) of nanobodies with target protein will be determined by crystallography. Candidate nanobodies will be labelled with fluorophores and applied in super-resolution cellular microscopy and immunohistochemistry. 

 Techniques covered includes molecular biology (DNA manipulation), protein expression and purification, biophysics (BLI, ITC, SEC-MALLS, SPR, Mass Photometry) and structural biology (X-ray crystallography or cryo-electron microscopy).

 Our lab has strong experience in hosting sandwich students with great outcomes.  The placement will equip the student with skills to confidently embark on a career in biological research.

Candidate background

The post holder should embody and demonstrate the Crick ethos and ways of working: bold, open and collegial. The candidate must be registered at a UK Higher Education Institution, studying in the UK and must have completed a minimum of two years’ undergraduate study in a relevant discipline, and on track to receive a final degree grade of 2:1 or 1. In addition, they should be able demonstrate the following experience and key competencies:

• The ideal candidate will be experienced in a laboratory environment with an interest in antibodies and structural biology.
• Good knowledge in relevant scientific area(s)
• Good written and spoken communication skills
• Ability to work independently and also capable of interacting within a group

References

1.         Han, X., Lu, X., Li, P.H., Wang, S., Schalek, R., Meirovitch, Y., . . . Lichtman, J.W. (2023)

            Preprint: Multiplexed Volumetric CLEM enabled by antibody derivatives provides new insights into the cytology of the mouse cerebellar cortex.

            Available at: BioRxiv. https://www.biorxiv.org/content/biorxiv/early/2023/05/21/2023.05.20.540091.full.pdf

2.         Bannas, P., Hambach, J. and Koch-Nolte, F. (2017)

            Nanobodies and nanobody-based human heavy chain antibodies as antitumor therapeutics.

            Frontiers in Immunology 8: 1603. PubMed abstract