Neurodegenerative diseases are a group of diseases characterised by progressive loss of
structure and function of neurons. Conditions under this umbrella tend to have two main
effects on patients, degeneration of motor function, and degeneration of cognitive ability.
Two diseases which are closely linked are Amyotrophic Lateral Sclerosis (ALS) which has
primarily motor effects, and frontotemporal dementia (FTD) which has primarily cognitive
effects. Despite their different presentations, both have been linked to dysregulation in RNA
binding proteins (RBPs). All of my work has sought to add to the existing body of knowledge
around how neurodegenerative diseases act and progress.
The main body of my work has sought to use RNA sequencing data to analyse data relating to
neurodegenerative diseases. 3 of the studies are relating to the effects on RNA expression
and splicing of mutations in C9orf72, TAU, FUS, and TARDBP. These chapters aim to further
elucidate how these genes function, either through analysing RNA expression in novel mouse
models, or by comparing RNA expression data from samples in the human brain biobank to
relevant controls. In them I find several promising candidates for further investigation with
regards to the changes which result from mutations in my genes of interest.
One other chapter uses RNA-sequencing data, and aims to compare data from a total RNAseq kit, and a kit produced by Lexogen which aims to be able to provide similar information
at a lower read depth as total RNA-seq data. While this was more a technical chapter, the
samples used were from FUS mutant mice and some of the results of analysis has been
published elsewhere. The final chapter involved creating a tool to analyse degeneration of
neuromuscular junctions using data from a tool created by a colleague.
Overall, my PhD thesis aims to move the field of research into neurodegenerative diseases
forward through a combination of improving our knowledge of diseases, improving our
knowledge of the tools we are using, and creating tools for use by future researchers.