2023 was an important year of reflection, both internally and externally. The Institute Assessment Exercise, where we outline our progress and future ambitions to our strategic funder BBSRC, provides the structure for this regular quinquennial review; a sort of science stock-taking exercise.
The overarching aim of our 2024-2028 research plans is to understand the cellular mechanisms that promote resilience across the life course. Lifelong health reflects successful adaptation to a lifetime of challenges (resilience) whilst the breakdown in physiology with age reflects failures in this adaption and/or maladaptive responses that can promote ageing, such as chronic inflammation.
Our future plans build on progress in uncovering the biological basis of ageing, set out new areas of discovery and define how our work is relevant to the global challenge of an ageing population. In this we align with the BBSRC’s Strategic Priorities of Ageing, Health across the Life Course and Bioscience for an Integrated Understanding of Health as well as wider government priorities for health.
How we operate to achieve this mission—our research culture—is equally important. Delivery of excellent science depends on the development and support for our people, a culture that supports innovation and collaboration, an outward-looking mindset and an inclusive community. Our vision for the Institute is to create a supportive and dynamic environment where people, ideas and research thrive.
Discovery research to underpin health innovations
Our three strategically-funded research programmes will leverage world-leading expertise and technical capabilities to make the discoveries that will ultimately feed forward into drug and vaccine development.
Research in our Signalling programme will identify new adaptive mechanisms to promote resilience to the collapse in proteostasis, damage to lysosomes and dysregulation of oxidant signalling; these stresses are all recognised 'drivers' of age-related functional decline and associated chronic illness.
Our Epigenetics research programme will define the role of intracellular metabolites in epigenetic resilience and adaptability, the factors controlling establishment and robustness of epigenetic states at key stages in development, how they adapt over the life course, and the potential for interventions that safeguard chromatin states.
Our Immunology programme will study the germinal centre response and the formation of B and T cell memory to shed new light on the decline in immunity across the life course and ways to mitigate this. A unique focus on RNA regulation in immune cell biology will enable innovations relevant to emerging therapeutics in this field.
Proteostasis across the life course – a unifying theme
One essential aspect of resilience is proteostasis: how the integrity of the cell’s protein production, regulation and disposal processes is maintained. Proteostasis breakdown is a lifelong challenge, a hallmark of ageing, a driver of age-related physiological decline and of age-related disease. Our 2023-2024 research plans incorporate proteostasis as a common, over-arching theme of the Institute’s three research programmes.
Our Signalling programme will define links between age-associated declines in poly-ubiquitylation and increases in protein aggregation at a proteome-wide level across organisms, tissues, sexes, and cell types, aiming to identify vulnerabilities in key protein quality control steps and signalling pathways that drive proteostatic breakdown.
Our Epigenetics programme will define how altered cellular metabolism impacts ageing phenotypes, in particular proteostasis, and whether developmental delay and metabolic disruption in early life predispose to loss of proteostasis in aged mouse tissues.
Our Immunology programme will study regulated mRNA translation and its adaptation to specific differentiated cell states such as antibody secreting plasma cells, part of a wider study of factors affecting resilience to withstand infection and the molecular mechanisms underlying inflammation.
Contributing to bioscience research and innovation ecosystems
Partnerships are key to our mission and consequently collaboration and knowledge exchange are central to our approach. The Institute remains integral to the success of the Babraham Research Campus (BRC), one of Europe’s most successful Innovation Campuses. Through a diverse range of interactions—collaborations, scientific services access, consultancies and training—the expertise of Institute staff supports commercial research on the Campus. In several instances we also lead culture change, such as through the Green Labs initiative and our LGBTQ+ Network.
The Institute is also active in bringing together and mobilising researchers across themes. In 2024 we led the creation of the UK Proteostasis Network; this makes connections that will accelerate our understanding of how proteostasis supports health but is also relevant to plant proteostasis and resilience of crops.
With our plans for 2024 to 2028 we are excited by the opportunity to expand our global collaborations, both with academic partners and commercially in the biotech and pharma sectors to accelerate the exchange and translation of our discovery research for public benefit.