Inflammation out of control: how dying cells drive disease

Project synopsis: Runaway inflammation kills millions of people every year and we still have very few drugs that stop it. This project tests whether a promising new class of anti-inflammatories works the way the field assumes it does. This project will use genetically modified mice and advanced microscopy to visualise the onset and resolution of inflammation in vivo. Project in more detail: Inflammation is how the body responds to infection and injury. Most of the time inflammation helps recovery and then switches off. However, when it does not switch off, the inflammatory response itself becomes the disease. Unrestrained inflammation is a central problem in ulcerative colitis, Crohn’s disease, sepsis, arthritis and many other prevalent human diseases. Accordingly, new ways to reduce excess inflammation are needed. One of the strongest triggers of inflammation is lytic cell death. This has led to the idea that stopping cell death could be effective anti-inflammatories. However, a deeper understanding of how cytoprotective drugs work is needed before they can be advanced clinically. This project will focus on a form of lytic cell death called necroptosis and aims to understand how anti-necroptotics reduce inflammation. This project will answer two fundamental questions: 1. Do anti-necroptotics reduce inflammation by stopping cell lysis? 2. What cells undergo necroptosis during inflammation and which cell types are rescued by anti-necroptotic therapy? Key techniques: • advanced intravital imaging • immunohistochemistry • in vivo mouse models of inflammation • cell culture • Western blotting Supervisory team: 1) Dr Andre Samson – Head of the Gut Inflammation Laboratory at the Centre for Inflammatory Diseases (Monash University) 2) Professor Connie Wong – Head of the Neuroinflammation Research Group and Deputy Director of the Centre for Inflammatory Diseases (Monash University) 3) Professor Edwin Hawkins – Laboratory Head at the Walter and Eliza Hall Institute of Medical Research and Head of the Colonial Foundation Diagnostics Centre Related work from the team: • Pang & Al-Ani et al., (2026) Science • Chiou S. et al., (2026) Cell Death & Differentiation • Chiou & Al-Ani et al., (2024) EMBO Molecular Medicine