Mansell - Innate Immunity, PRRs & Inflammation

Although NLRP1 was the first inflammasome ever discovered, its role in human disease has remained elusive—until now. This cutting-edge research project dives into the emerging world of human-specific NLRP1 variants, which are uniquely expressed in barrier cells like keratinocytes and mucosal epithelial cells. By characterising patient-derived mutations and exploring NLRP1’s response to viral threats such as Dengue, Zika, Herpes, and Influenza, we aim to uncover its hidden potential in immune defense.

Our team will also pioneer the use of the world’s first ‘humanised’ NLRP1 mouse model and test the only known NLRP1 inhibitor to target inflammation at its source. These groundbreaking studies promise to redefine our understanding of NLRP1 biology and open new doors to anti-inflammatory therapies that could transform treatment for a range of infectious and inflammatory diseases.

Ever wondered why a regular flu might leave you in bed for a few days, but avian flu can be deadly? Or why COVID-19 caused such severe lung damage, while other coronaviruses just gave us a mild cold? The answer may lie in how certain viruses behave inside our cells.

Our research has uncovered that some dangerous viruses—like severe strains of influenza, SARS-CoV-2, and Hendra virus—form clumps of viral proteins, called aggregates, when they infect human cells. These aggregates trigger a powerful immune reaction by activating a protein complex known as the NLRP3 inflammasome. This leads to a flood of inflammatory signals that can worsen disease symptoms and outcomes.

This project will explore how these viral aggregates form, how they activate inflammation, and whether we can use them to predict which viruses might become more dangerous in the future. We’re also investigating ways to block this overactive immune response, potentially paving the way for new treatments that reduce the severity of viral infections and help people recover faster.

This innovative research project explores the dynamic interplay between bacteriophages (viruses that infect bacteria), parasitic bacteria, and the human immune system. Led by A/Profs Mansell and Steve Petrovski, the team investigates how bacteriophages can influence immune responses and potentially disrupt harmful bacterial infections. Mansell’s expertise in inflammasomes and Toll-like receptors and innate immunity complements Petrovski’s pioneering work in phage biology and microbial genetics, creating a unique opportunity to understand how phages or parasitic bacteria intersect with the immune response to modulate inflammation.

Characterising these interactions, will uncover new strategies for controlling bacterial pathogens—especially those resistant to antibiotics—through phage therapy, 'hunter-killer' bacterium and immune modulation. This research could pave the way for novel treatments that harness the natural enemies of bacteria to reduce inflammation and improve outcomes in infectious diseases.

Did you know your immune system runs on energy just like your muscles do? The field of immunometabolism explores how immune cells use energy to fight infections—and what happens when that process goes wrong. When metabolism is disrupted, it can lead to chronic inflammation and disease. Our research focuses on a key player in this process: a protein called STAT3, which helps immune cells like macrophages control their energy production through tiny powerhouses called mitochondria.

Building on our earlier discoveries, this project dives deeper into how STAT3 influences mitochondrial function, especially how disruption of the Electron Transfer Chain and metabolites leads to regulation of inflammatory cytokines—a vital part of how cells breathe and generate energy. By understanding these mechanisms, we hope to uncover new ways to fine-tune immune responses and develop next-generation therapies that target inflammation at its source.