What lies in the hearts of mice?
Funding from the Nuffield Foundation enabled Sarah Hutton, an S5 pupil from Gracemount High School, to undertake a four-week Nuffield Research Placement: July 2017
Funding from the Nuffield Foundation enabled Sarah Hutton, an S5 pupil from Gracemount High School, to undertake a four-week Nuffield Research Placement in Professor Cathy Abbott’s lab in the Centre for Genomic and Experimental Medicine (CGEM) throughout July 2017.
Sarah’s project was created by Fiona McLachlan, a PhD student in Professor Abbott’s Research Group, whose first lab experience was also due to a Nuffield Research Placement award with Professor Cathy Abbott’s lab! Fiona went on to do a 4 year degree in Manchester but secured her PhD studentship back at CGEM.
The purpose of Sarah’s molecular genetics project, aimed at studying mutations that cause epilepsy, intellectual disability and heart disease, was to determine the extent of problems with protein translation in mice that have mutations within the EEF1A2 gene. Sarah focused on cells within the brain and heart as previous research has suggested that these organs are affected by these mutations.
The EEF1A2 gene encodes a protein that assists in DNA translation - the process of creating other proteins from DNA templates. If the process of translation is impaired, this can result in damaged or incorrectly folded proteins that do not function properly. An accumulation of these proteins inside the cell leads to the activation of the unfolded protein response, which aims to correctly fold damaged proteins, or tag them with ubiquitins that mark them for degradation.
Compared to the hearts of mice with no eEF1A2 mutations, Sarah found higher levels of ubiquitins in the hearts of mice that carry mutations in this gene. This suggests that mutations within this gene can indeed lead to poor quality protein translation. Follow-up studies could test whether this is also the case in other organs, as well as checking whether the unfolded protein response is upregulated with age.