Grant: Project Grant

Nearly all life forms on earth require iron to survive. Iron is important for many functions in our body, and probably best known for its role in transporting oxygen, allowing us to breathe. Once oxygen is taken up through the lung, it is transferred to an iron atom that sits at the centre of a special molecule called heme. The heme molecule itself is docked to a larger structure called hemoglobin, and together, they deliver oxygen to where it is needed via the bloodstream. These heme groups are also important for other processes in our cells, including the removal of harmful substances and the production of steroid hormones, like the famous testosterone. The King-Jones lab uses the fruit fly as a model to study undiscovered aspects of iron biology. For instance, they discovered that steroid hormone-producing cells have a high demand for iron and heme. Importantly, King-Jones and colleagues realized that they can take advantage of these cells to learn new things about how humans regulate their iron "balance sheet". Since both too much and too little iron can cause severe diseases in humans, it is essential that we learn more about how iron handled in our bodies, and how this is regulated. Using a range of genetic tricks, King-Jones and colleagues have recently discovered more than 20 genes with unexpected roles in regulating and balancing appropriate iron levels. The proposal focuses on the so-called "Iron Regulatory Protein 1" (IRP1) and how it regulates genes important for the safe handling of iron. The King-Jones lab has shown that IRP1 regulates more genes than previously thought and that this occurs by new, unexpected mechanisms. The study of these new, unexpected aspects of iron biology will improve our understanding of diseases that are caused by too much or too little iron.