Illuminating fragmented ribosome assembly in the human parasite Toxoplasma gondii

All cells are dependent on the continuous assembly of ribosomes to survive. This assembly process dates back to the last universal common ancestor, 4 Billion years ago. This process is co-transcriptional and fully dependent on the ribosomal RNAs being two separate, continuous molecules. However, recent structures of “fragmented” ribosomes built from many smaller independent rRNAs, referred to as rRNA fragments, have raised questions as to the universality of this process. How cells overcome the challenges fragmented rRNA poses to ribosome assembly is wholly unstudied, yet a central question for one of the most essential objects in biology. Here I propose to investigate the essential assembly of fragmented mitochondrial ribosomes in the human parasite Toxoplasma gondii, containing a total of 53 rRNAs, the most extensive fragmentation known. My research will achieve two aims; 1) Provide structural and mechanistic descriptions of fragmented rRNA assembly via single particle electron cryomicroscopy and mass spectrometry. 2) Reveal driving forces and constraints on the evolution of rRNA fragmentation across the broader group Mysozoa, through bioinformatics and phylogenetics. Through this research I aim to characterise an completely undescribed process in biology with central relevance to mitochondrial function, the parasitology of Toxoplasma, and the evolution of the ribosome.