Towards the automated optimisation of protein labelling methods

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.

The CDT in Molecules to Product has the potential to make a real impact as a consequence of the transformative nature of the underpinning 'design and supply' paradigm. Through the exploitation of the generated scientific knowledge, a new approach to the product development lifecycle will be developed. This know-how will impact significantly on productivity, consistency and performance within the speciality chemicals, home and personal care (HPC), fast moving consumer goods (FMCG), food and beverage, and pharma/biopharma sectors.
UK manufacturing is facing a major challenge from competitor countries such as China that are not constrained by fixed manufacturing assets, consequently they can make products more efficiently and at significantly lower operational costs. For example, the biggest competition for some well recognised 'high-end' brands is from 'own-brand' products (simple formulations that are significantly cheaper). For UK companies to compete in the global market, there is a real need to differentiate themselves from the low-cost competition, hence the need for uncopiable or IP protected, enhanced product performance, higher productivity and greater consistency. The CDT is well placed to contribute to addressing this shift in focus though its research activities, with the PGR students serving as ambassadors for this change. The CDT will thus contribute to the sustainability of UK manufacturing and economic prosperity.
The route to ensuring industry will benefit from the 'paradigm' is through the PGR students who will be highly employable as a result of their unique skills-set. This is a result of the CDT research and training programme addressing a major gap identified by industry during the co-creation of the CDT. Resulting absorptive capacity is thus significant. In addition to their core skills, the PGR students will learn new ones enabling them to work across disciplinary boundaries with a detailed understanding of the chemicals-continuum. Importantly, they will also be trained in innovation and enterprise enabling them to challenge the current status quo of 'development and manufacture' and become future leaders.
The outputs of the research projects will be collated into a structured database. This will significantly increase the impact and reach of the research, as well as ensuring the CDT outputs have a long-term transformative effect. Through this route, the industrial partners will benefit from the knowledge generated from across the totality of the product development lifecycle. The database will additionally provide the foundations from which 'benchmark processes' are tackled demonstrating the benefits of the new approach to transitioning from molecules to product.
The impact of the CDT training will be significantly wider than the CDT itself. By offering modules as Continuing Professional Development courses to industry, current employees in chemical-related sectors will have the opportunity to up-skill in new and emerging areas. The modules will also be made available to other CDTs, will serve as part of company graduate programmes and contribute to further learning opportunities for those seeking professional accreditation as Chartered Chemical Engineers.
The CDT, through public engagement activities, will serve as a platform to raise awareness of the scientific and technical challenges that underpin many of the items they rely on in daily life. For example, fast moving consumer goods including laundry products, toiletries, greener herbicides, over-the-counter drugs and processed foods. Activities will include public debates and local and national STEM events. All events will have two-way engagement to encourage the general public to think what the research could mean for them. Additionally these activities will provide the opportunity to dispel the myths around STEM in terms of career opportunities and to promote it as an activity to be embraced by all thereby contributing to the ED&I agenda.