Grant: Project Grant

Peroxisomes are a critical component within each of the trillions of cells that make up the human body. Within each of our cells, peroxisomes act like tiny factories that ensure availability of chemical building blocks that cells need to function properly. Making new peroxisomes is a critical function needed during fetal and early child development. The formation of new peroxisomes is controlled by our genes, which can become defective in a process called mutation. Children inheriting mutations in any one of the core genes that make Peroxins, proteins that are needed to make new peroxisomes, are born with defects in multiple organs like the brain, kidney, and liver. The most severe of Peroxin gene mutation linked disease is Zellweger spectrum disorder, which is often fatal early in life. Those children that do survive require constant care, placing a significant burden on them, their families, and the healthcare system. What is currently missing is critical fundamental knowledge of how peroxisomes contribute to the overall availability of fat molecules during early child development. Without better understanding of this process, it will be difficult, if not impossible, to improve the few and ineffective treatments available. We found that some Peroxin genes also have a second job storing fat molecules. We are trying to understand how this coordinates chemical conversion of fat molecules with storage, and how this supplies these molecules during development of the brain. It is also possible that this coordinating function in one organ supplies molecules via the bloodstream to the brain. We will examine cells within the developing brain, fat tissue, or liver of simple laboratory animals (fruit flies) to understand how Peroxin gene mutations affect this coordinated process. Improved understanding here will assist ongoing efforts to identify new treatments based on supplying missing molecular building blocks in the right organs at the right time of child development.