Development of a Chemoproteomics Centre of Excellence: A Prosperity Partnership for Drug Discovery in Northern Ireland

In this BBSRC Prosperity Partnership, Queen's University Belfast (QUB) and Almac Discovery will bring together their joint expertise to create a new state-of-the-art Chemoproteomics Centre of Excellence situated within QUB; this will be the first of its kind in the Northern Ireland region. Specifically, we will use the Prosperity Partnership to co-develop a new mass spectrometry proteomics facility that can study molecular changes in proteins from cells and tissues treated with therapeutic drugs and drug-like molecules ("chemical probes"). This facility builds on a well-established relationship between the partners in basic biological research and early-stage drug discovery (Almac), leveraging the capabilities and state-of-the-art expertise of QUB researchers in mass spectrometry and basic and translational biological research (namely inflammation, cell death and ion channels) across three University Research Centres (Cancer, Experimental Medicine and Pharmacy).

The Centre of Excellence will provide completely new chemical tools that will open new areas of biology and a mass spectrometry platform that will benefit both partners, thereby enabling cutting-edge biological research and drug discovery. It is also envisaged that this facility will provide opportunities for other collaborators, both academic and industrial, to advance their basic research and R&D portfolios, providing a business model that will ensure that this Centre of Excellence will continue to support academic and industrial R&D in the region beyond the life of this project. Not only will the Centre of Excellence enhance our regional capabilities, it will also provide skills training for apprenticeships through to doctoral researchers and create value in the forms of new drugs, intellectual property and high quality academic publications (reputation). Thus, the Centre of Excellence will encourage inward investment and sectorial growth in Northern Ireland, helping to "level up" the capacity and contribution of the Northern Ireland Life Sciences sector to the broader UK economy. This is in line with both regional (10X economy, Department for Economy) and Life Sciences Vision (UK) strategies.

Our ultimate vision is to build an internationally recognised regional resource whose chemical probes, experimental capabilities, knowledge and expertise can assist the research and development programmes of other regional, national and international industrial and academic partners. Thus, the creation of this industry-facing, University-based facility represents a unique opportunity to provide a step-change in proteomics-based experimental capabilities in Northern Ireland.

This Prosperity Partnership represents the start of a completely new collaborative R&D programme between Queen's University Belfast and Almac Discovery. Binding of small molecules to target proteins can induce changes in protein conformation, its interactome and functional state, potentially resulting in stabilisation or degradation of partner proteins, changes in subcellular localisation and altered downstream signalling. Genomic profiling approaches to better understand biology are mature and continue to advance rapidly; however, these approaches are not capable of assessing the functional state of the proteome with respect to perturbations induced by small molecule inhibitors. Recent advances in the sensitivity, depth of coverage, and quantitative robustness of mass spectrometry-based proteomics now positions it as a critical emergent tool in chemical biology and medicinal chemistry. In this proposal, we will establish an advanced mass spectrometry chemoproteomics platform that exploits and further develops the latest advances in Data Independent Acquisition Mass Spectrometry (DIA-MS), incorporating high throughput approaches. We will use this platform to identify and profile chemical probes which perturb protein target networks in relevant models. Our ultimate vision is to build an internationally recognised regional resource whose chemical probes, experimental capabilities, knowledge and expertise of physiologically-relevant biological models can assist other regional, national and international industrial and academic partners in research and development focused on previously undruggable targets.