post-transcriptional regulation of gene expression following toxic injury

DNA is the 'code of life' storing all the instructions a cell needs, however the information contained in DNA needs to be translated to produce functional proteins. To achieve this an intermediate message, called messenger RNA (mRNA), is generated from the DNA, which is then "read" by large, complex machines called ribosomes, that act as translators travelling along the mRNA reading the instructions of how to build specific proteins. Following exposure to both environmental and therapeutic compounds mRNA can be damaged, and this can result in the misreading of the mRNA by ribosomes or the ribosomes stalling on the mRNA and colliding. Such ribosome collisions are "sensed" by the cell and this activates a number of different cell stress pathway but in particular the ribosome stress response. The aim of this project is to understand more precisely how the ribosome stress response is triggered. This work is important to human health since certain advanced therapeutics contain mRNA, for example the COVID-19 mRNA vaccines. Knowledge from this work will help us to understand how modified mRNAs in vaccines affect such cellular processes, and so can inform the safe design of these new therapeutics.