Grant: Project Grant

Ribosomes are the cellular protein synthesis machinery, and highly conserved from bacteria to humans. They are complex molecular machines made up of four ribosomal ribonucleic acids (rRNAs) and 80 ribosomal proteins. Until recently it was believed that ribosomes are the exact same in every single cell within an organism, from a liver cell to a neuron. However, recent studies showed that there exists a small pool of 'specialized' ribosomes that can be found either in specific cells or tissues, such as testis or oocytes, and which appear to be involved in the biosynthesis of very specific proteins. Moreover, genetic mutations in components of ribosomes, resulted in highly specific diseases affecting the blood, skeleton or cancer predisposition, and established themselves often during early development, suggesting that these components, and 'specialized' ribosomes, may have an important role. While some of the differences between 'normal' and 'specialized' ribosomes have been uncovered, the proteins they are to synthesize as well as how specialized ribosomes are produced and fine-tuned themselves have not. Ribosome biogenesis, the process of making ribosomes, involves the coordinated function of over 200 proteins, and understanding the mechanisms that define making and function of specialized ribosomes will be of great importance to understand human development and disease on a molecular level. The main aim of the proposed research is to determine the events that distinguish different populations of ribosomes and their activity within different cell and tissue types. This will allow us to gain insight into how specialized ribosomes, and mutations within them, can affect the development of certain diseases as well as the fate of cells and organs during human development as a whole.