NorthWest Biosciences

Illuminating fragmented ribosome assembly in the human parasite Toxoplasma gondii

Supervisors 

Dr Victor Tobiasson, University of Glasgow

Prof Simon MacKay, University of Strathclyde

Prof Kostas Tokatlidis, University of Glasgow

Summary

The ribosome, the RNA-protein machinery responsible for protein synthesis, is among the oldest and most conserved structures in biology. At more than 4 billion years old it predates even the oldest rocks on planet Earth. Over the course of 4 billion years, life has developed into the diverse lifeforms we see around us. However, despite the diversity of life, the ribosomes of all living organisms closely share the same general structure. Additionally, the process of building new ribosomes, ribosome assembly, is thought to be universally conserved. The exception to this rule resides in the mitochondrion, the ancient endosymbiotic organelle responsible for energy conversion in Eukaryotes where the forces of evolution have drastically altered the composition of the ribosome.

Recently we characterized the structure of a highly unusual mitochondrial ribosome from the human parasite Toxoplasma gondii. Here, rather than the standard two large pieces of RNA, the ribosomes contain 53 smaller pieces, known as fragments. How this fragmented ribosome is assembled is completely unknown, and no conceptual models even exist. It is a huge fundamental mystery in biology which this PhD project aims to tackle. Using both cryoEM and bioinformatics, this project will characterize the structure, assembly, and evolution of this fragmented ribosome to try to further understand one of the most ancient and central biological machines on earth.