Innate immune responses vary substantially between individuals and strongly influence infection outcomes, transmission risk and responses to vaccines and therapeutics. This project will develop scalable in vitro models that mimic infection using pattern-recognition receptor agonists targeting pathways such as TLRs, STING and cytosolic nucleic-acid sensors. Using primary human immune cells, whole-blood systems and trained-immunity models, the student will characterise cytokine production, inflammasome activation, complement activity and immunometabolic responses. Inter-individual variability will be mapped to define immune-response archetypes associated with protective, exaggerated or dysregulated responses. The project will then investigate whether these immune states can be selectively reprogrammed using small molecules and vaccine-relevant stimuli. A major innovation is the concept of sustained viral resilience, where transient modulation of innate pathways induces durable antiviral protection through metabolic and epigenetic mechanisms.
This PhD studentship is part of an Integrated Health Security Cohort. Building on The Pandemic Institute’s strategic partnerships with UK Health Security Agency (UKHSA), NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (HPRU EZI), and Defence Science and Technology Laboratory (Dstl).
