Towards the automated optimisation of protein labelling methods

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The objective of the project is to develop autonomous, self-optimising approaches towards modified biopharmaceuticals. This will be achieved by development of a liquid-handling system for reaction sampling, together with a software platform for automated analysis of reaction.Aims: 1. Develop a computational platform for automated deconvolution, integration and kinetic analysis of MS-based protein-labelling data. 2. Develop a liquid-handling approach for automated reaction set-up and sampling of protein-labelling approaches. 3. Develop a computational approach to identify and optimise reaction conditions for automated reaction optimisation by linking aim 1 and 2. Methodology:The initial planned approach to reaction optimisation is to use solid-phase extraction approaches to automatically sample and prepare fixed-time reaction samples. These samples (in a 96-well plate format) will then be directly analysed via MS before automated deconvolution, integration and quantification. Reaction sample data will be automatically integrated into a software package for kinetic analysis and subsequent optimisation of reactions to obtain the highest quality product while using minimal reagent quantities. A range of protein modification reactions will be used, initially exemplified by the use of recently-developed peptide-ligase-based methodologies at the University. During the project, it is anticipated that the system will be applied to a variety of novel variant protein modification methods to exemplify the approach further. Potential Impact:The project will develop a generic platform technology for the optimisation of protein-small molecule conjugate production. The approach is designed to be agnostic to both the protein and small molecule target and will therefore be transferable to any new biopharmaceutical preparation method. Rapid optimisation using this approach will reduce both the costs of optimisation and also provide economic advantages in terms of tightly defining reaction parameters required for production as well as defining attributes which can be used as part of the product specification for IP purposes.