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

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/