Fundamental mechanisms controlling human energy homeostasis

The human brain's appetite control centre is failing in people with severe obesity, and this project will map exactly how those neural circuits break down. Obesity and its consequences—type 2 diabetes, heart disease, and several cancers—create a massive health burden, yet the fundamental biological wiring that balances food intake against energy expenditure remains poorly understood. This research targets that gap by studying people at both extremes of weight: those with severe obesity and those who remain naturally thin. Using genetic data and stem-cell-derived human brain cells, the team will trace the molecular networks that converge on leptin-melanocortin signalling, a key pathway that tells the brain whether the body has enough energy stored. This is fundamental science with no immediate clinical product. The goal is to identify precise control points within human energy homeostasis—specific molecules or cellular steps that could one day be targeted by drugs. If successful, the work would provide a molecular roadmap for developing therapies that restore normal appetite regulation, rather than simply managing obesity's downstream effects. Similar fundamental mapping of metabolic pathways has previously enabled treatments for rare genetic obesity disorders.