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Advancing our understanding of the molecular and cellular basis of immunity to protect and improve health across the life course.

Promoting immunity is one of the pillars of lifelong health and one of the best interventions we have in a world at risk of losing effective antimicrobials. A decline in immunity, experienced as a greater number or more severe infections and a longer recovery time, is one of the most widely recognised consequences of ageing. Our core immunology research has two overarching aims interfaced around the problem that as we age, protective immune responses wane and susceptibility to age-related inflammatory damage increases. Both of these may be addressed by therapeutic interventions but to develop these interventions, we need a better understanding of the molecular and cellular basis of adaptive immunity.

Our discoveries will pave the way to new approaches, including vaccines, small molecules and biological/cellular therapeutics, to reduce susceptibility to infectious and other diseases and their impact. By diminishing the occurrence of chronic multimorbidities, these interventions will deliver health, social and economic benefits.

Aim 1: Understanding the molecular and cellular basis of immunity
Improved vaccine design and immunisation strategies require a deeper understanding of the fundamental molecular and cellular basis of immunological memory. A productive immune response requires the collaborative efforts of many different cell types that must be coordinated in both time and space. Our first aim is to understand the mechanistic principles which direct the quality and durability of the adaptive antibody and cellular immune responses. Our work towards this aim will identify the key cellular and molecular requirements of an effective response to vaccines over the life course.

Aim 2: Mechanisms of resilience and repair
In our second aim we will work to deliver new insight into why older bodies are less resilient to the impacts of respiratory infection than younger ones. Resilience is the ability to withstand infection and to restore or repair function after infection. In older people, pathogens that infect the respiratory system are major causes of morbidity and mortality.

Applying new high-dimensional sequencing and imaging technologies, we will characterise how ageing alters the immune response to respiratory infection, with a focus on the localisation and persistence of immune cells in the lungs. This work will identify the factors involved in immune cell migration to the lungs and their retention during respiratory infection.

A parallel strand of work will explore the molecular mechanisms underlying inflammation, a hallmark of ageing. Infection-induced immunopathology is dangerous at any age but appears to disproportionately affect older individuals, leading to reduced disease tolerance. We will apply a multidisciplinary approach to explore whether T cell ageing contributes to inflammation.