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Development of a synthetic platform to derive small antibodies against user-defined ligands

  • Full or part time
    Dr E Cachat
    Prof S Rosser
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Advances in recombinant antibody technologies have greatly facilitated the development of novel antibody formats such as single-chain variable fragments (ScFvs) [1] and single domain nanobodies [2]. These versatile protein binding molecules combine high specificity and affinity, and are rapidly emerging as essential research, diagnostic and therapeutic tools. In the field of synthetic biology, these small antibody molecules are increasingly used as orthogonal binding domains to engineer cells with novel sensing capabilities. Unfortunately, ScFvs/nanobodies against user-defined ligands are not easily derived: to avoid the cumbersome immunisation route, researchers turn to synthetic display libraries panned against immobilised ligands to select for high binders [3]. This process still presents many difficulties and in particular for antigens that are not easily purified or do not maintain their native conformation once solubilised. The aim of this project is to develop a modular ScFv/nanobody generating platform that encompasses different antibody formats, display systems, antigen presentation methods, etc. to streamline antibody fragments generation and optimisation.

The student will (i) work in close collaboration with the Edinburgh Genome Foundry (Edinburgh) to develop synthetic antibody libraries, (ii) engineer different cell chassis (bacteria, yeast and mammalian cells) to develop and test appropriate biopanning methods, and (iii) liaise with other researchers at the University of Edinburgh to identify antigen targets of importance for the biomedical field.

Host lab: https://www.ed.ac.uk/profile/elise-cachat
Edinburgh Genome Foundry: https://www.genomefoundry.org/home
SynthSys: http://www.synthsys.ed.ac.uk/


Funding Notes

The “Visit Website” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will provide a list of funding options and guide you through the application process.

If you would like us to consider you for one of our scholarships you must apply by 5 January 2020 at the latest.

References

[1] scFv antibody: principles and clinical application. Ahmad ZA et al. Clin Dev Immunol. 2012:980250.
[2] Nanobodies as therapeutics: big opportunities for small antibodies. Steeland S et al. Drug Discov Today. 2016; 21(7):1076-113.
[3] Yeast surface display platform for rapid discovery of conformationally selective nanobodies. McMahon C et al. Nat Struct Mol Biol. 2018; 25(3):289-296.

How good is research at University of Edinburgh in Biological Sciences?

FTE Category A staff submitted: 109.70

Research output data provided by the Research Excellence Framework (REF)

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