UKProNet2025

Proteins orchestrate all of life’s functions. All organisms dedicate a large proportion of their resources to evolutionarily conserved mechanisms of protein homeostasis (“proteostasis”), an umbrella term that describes the synthesis, folding, trafficking and degradation of proteins. These conserved protein quality control (PQC) processes are coordinated across biological scale (from molecules, organelles, cells, tissues, to organismal level) and are critical to enable responses to physiologic and stress-related cues. It is increasingly apparent that a deep understanding of proteostasis and how it can be leveraged is critical to tackle humanity’s major challenges: Ageing and Health. PQC declines with age, causing accumulation of toxic protein aggregates that drive normal ageing and its pathologies (e.g. neurodegeneration). Strategies to mitigate this PQC failure are urgently required. Emerging targeted protein degradation technologies provide new therapeutic horizons for disease. To fully exploit these mechanisms requires a deep understanding of PQC systems, combined with novel synthetic biology approaches that leverage proteostasis mechanisms from other species. Food security. Strategies to improve crop yields, nutritional quality, resilience to pathogens and climate change are critical for the health of the growing global population. The importance of proteostasis in plants is exemplified by the extraordinary number of genes dedicated to PQC in crop genomes compared to humans. These genes, which have evolved to deal with pathogens and environmental stresses, provide a rich opportunity to engineer plants/animals with improved resilience/yields. Barriers to progress. These key scientific areas require, and are fertile ground for, cross-disciplinary and cross-sector collaboration and innovation. The UK has excellent strengths in proteostasis research, but these are siloed into smaller communities with limited intercommunication. There is clearly a strong case for a well-integrated overarching community with a bold vision to be world leading in this crucial field of biology. To overcome these barriers, the UK Proteostasis Network (UKProNet) will address three key objectives: Objective 1. Integrate the UK Proteostasis communities to drive a holistic understanding of proteostasis across biological scales and model systems by promoting integration between research silos and sectors (academia and industry). A primary goal for UKProNet, identified via a community survey, is to enhance uptake of foundational and evolving technologies including artificial intelligence (A.I.). Objective 2. Empower the community to tackle key societal challenges by leveraging proteostasis across kingdoms of life to enhance adaptations to proteostasis challenges and organismal resilience across the lifespan. Objective 3. Strengthen the national and international profile of UK Proteostasis by enhancing our visibility on-line (through website provision, social media, newsletters, protocol and reagent database), early career researcher (ECR) support and at high-profile annual meetings. To achieve these goals, we will run community-led workshops (to disseminate key proteostasis technologies and A.I.), provide pump-priming grants, lab exchange awards and summer studentships. A dedicated, well-funded ECR committee will develop a strategy to ensure that the leaders-of-tomorrow have a central role in shaping the proteostasis landscape. Our activities will promote an inclusive environment where people from marginalised or underrepresented groups can feel empowered to lead and drive best practices in equality, diversity and inclusion. A UKProNet steering group of elected community members, plus an external advisory board (diverse in gender, career stage and lived experience) will provide ongoing monitoring and advice on strategy and evaluation. Together we will build upon the UKs expertise to develop a thriving, world-leading community of proteostasis researchers.