Structure and composition of specialised ribosomes

Until recently it was thought that all ribosomes were the same, but substantial new evidence has revealed that ribosome heterogeneity provides an additional level of translational control. These different ribosome populations are termed ‘specialised ribosomes’. This project aims to understand the structural consequences of specialisation, using a cuttingedge combination cryo-EM and mass spectrometry. A related project will focus on the translational consequences of specialisation. These two projects combined will allow us to understand how structure enables ribosomes to translate specific mRNA pools.
We have discovered differences in ribosome composition in several Drosophila melanogaster tissues, including testis. mRNA translation is particularly important during sperm production so it will be exciting to understand how this novel mechanism of gene regulation is achieved and how it contributes to, e.g., male fertility.
To understand changes to ribosome structures this project will involve cryoEM, to resolve the structure of the ribosome at close-to-atomic resolution; quantitative mass spectrometry, to identify and quantify protein composition of the whole ribosome population; and native mass spectrometry, to gain detailed insight into the composition of specific ribosome populations. This work has potential to shed light on the underlying mechanism of human diseases caused by mutations to ribosomal proteins e.g. Diamond-Blackfan.