Ribosome biogenesis is the process responsible for correctly assembling ribosomal RNAs and ribosomal proteins into functional, translation competent ribosomes. This is one of the most energy consuming processes in a cell that takes place in the nucleolus, the nucleoplasm and the cytoplasm. In addition to their structural function in mature ribosomes, ribosomal proteins also play important roles in ribosome biogenesis. Mutations in various human ribosomal proteins have been reported to result in diseases like bone marrow failure syndromes, making ribosomal proteins and their involvement in ribosome biogenesis an interesting subject to study. Up to now, for only few ribosomal proteins detailed functions in ribosome biogenesis have been described. The aim of the proposed project is to investigate the function of Rps15, a ribosomal protein of the small (40S) ribosomal subunit, in ribosome biogenesis. The studies will be performed in the yeast Saccharomyces cerevisiae, which is due to the combination of powerful genetic and biochemical methods the most commonly used and best studied model organism for eukaryotic ribosome biogenesis. In preliminary experiments, we identified Rps15 as a genetic interaction partner of a known 40S maturation factor, suggesting it could also be involved in ribosome biogenesis. Our current hypothesis based on preliminary data as well as the recently published crystal structure of a eukaryotic 40S subunit predicts that Rps15 is involved in a structural re-arrangement that takes place in a late stage of 40S biogenesis. The characterization of Rps15 in the course of this project will include the generation of various mutants, and their phenotypic investigation in respect to defects in late 40S biogenesis. Especially, we will put efforts in identifying and characterizing structural differences of 40S subunits in the mutants as compared to wild-type cells. The proposed experiments will allow us to gain an understanding of the role of Rps15 in the ribosome biogenesis process. Furthermore, the characterization of the role of Rps15 in structural re-arrangements during the 40S biogenesis pathway would be an important step to a better understanding of the structural changes ribosomal particles undergo in course of their maturation. Further, as Rps15 is highly conserved from yeast to human, our results will also help understand the function of the human orthologue, and might in the end contribute to a better understanding of the link between ribosome biogenesis defects and diseases.