Molecular regulators of the alarmin IL-33 in health and disease

A single protein, IL-33, controls how the body reacts to threats as diverse as parasitic worms, obesity, allergies, and Covid-19, yet scientists do not fully understand how it works or why its effects vary so dramatically between tissues. IL-33 is a cytokine—a signalling molecule that rallies immune cells. It is already the target of experimental drugs for asthma and inflammatory disease. But the protein has a puzzling double life: it breaks down within minutes of release, yet can trigger long-lasting responses far from its source. Immune cells in the gut barely respond to it, even though gut parasites are exquisitely sensitive to IL-33 signals. This project will solve three specific puzzles: how parasite proteins block IL-33 at the structural level, what IL-33 does when released from the intestinal lining into the body during obesity, and whether a soluble form of the IL-33 receptor stabilises the protein and carries it to distant sites. The research is fundamental science. It uses structural biology, genetically modified mice, and human tissue cultures to map the molecular rules governing IL-33 behaviour. If successful, it could explain why anti-IL-33 drugs work in some tissues but not others, and reveal whether blocking or boosting IL-33 in specific locations—rather than throughout the body—could treat allergies, metabolic disease, or parasitic infections more effectively.