Funding outcome

Every cell in the human body plays a specific role to keep us healthy. Similarly, cells contain different parts, called organelles, which work together to keep our cells healthy. For instance, peroxisomes are 'tiny factories' that produce the building blocks cells need to survive, such as fat molecules. During fetal and early child development, new peroxisomes are made to support the growing nutritional needs of cells. The instructions for making peroxisomes are encoded in our Peroxin (PEX) genes. However, these genetic instructions can become unreadable due to mutations. Inherited PEX mutations impair brain, kidney, and liver development in children. In severe cases, this leads to Zellweger spectrum disorder (ZSD), a developmental disorder that can be fatal in early life. Children who survive with ZSD have limited functional independence and intellectual disability, which impacts themselves, their families, and the healthcare system. Despite a common diagnosis, children with ZSD have diverse symptoms due to their unique mutation(s). This makes treatment difficult, as we do not fully understand how peroxisome dysfunction impairs cell birth and growth. One hypothesis is that PEX mutations also affect lipid droplets - organelles that store fat. We have found that PEX genes encode instructions for lipid droplet function. During development, peroxisomes and lipid droplets may work together to supply essential fat molecules to cells. To understand how PEX mutations affect this process, I will examine cells in the developing brain, fat tissue, or liver of mutant fruit flies and compare them to healthy flies. Juvenile fruit flies are commonly used as models of early child development. My research will help us understand how problems with peroxisomes and lipid droplets lead to childhood intellectual disability. It will also inform new treatments to supply missing molecular building blocks, in the right organs, at the right time - to ensure healthy child development.