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DC11: MARINE GUINGAND (FR)

Partner of attachment: RFI (Rosalind Franklin Institute) UK

 

Supervisor: Prof. Ben DAVIS (Mentor: Dr. Adeline POH)

 

University of Attachment: UOXF (University of Oxford) UK

 

Director of Thesis : Prof. Ben DAVIS

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One of the main challenges in protein radiolabelling relies on the late-stage and site-selective incorporation of radioisotopes in a straightforward and traceless manner. Indeed, the chemistry behind it usually involves time-consuming and multi-step synthesis to produce large radioactive carriers, which could impact protein integrity. In our project, we aim to build a new methodology that is universally compatible with short-lived isotopes such as fluorine 18 while being highly flexible to be applicable to any protein with minimal alteration of protein integrity. We articulate our approach around three main objectives: 1) The development of reagents for efficient protein radiolabelling under biological conditions; 2) The creation of radiolabelled proteins retaining both protein functions and structure; and 3) Performing protein radiolabelling directly in living systems.

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Since the project started, we have managed to mutate and express a diverse set of proteins, which are used as protein models to explore their compatibility with our method. From a chemical point of view, we designed and synthesised six ‘cold’ small molecules mimicking radioactive reagents. Upon optimisation, our method enables high conversion into ‘cold’ modified proteins under biocompatible conditions (> 80%) while retaining protein integrity. This first successful achievement led to the investigation of the synthesis of radioactive precursors to produce their radioactive protein counterparts.

 

The method investigated in this project would enable the precise radiolabelling of a wide range of proteins while maintaining their natural properties. With such constructs, the generation of radiolabelled protein would be greatly improved, both in methodology and quality, for protein radiolabelling studies in living systems.

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