Amy Wolstenholme

PhD thesis: Characterisation of C9orf72 repeat instability and somatic mosaicism in ALS / FTD

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two devastating neurodegenerative disorders. An unstable repeat expansion in the gene C9orf72 is the most common genetic mutation linking these two diseases, however characterisation of the repeat expansion is still in its infancy. My PhD focuses on investigating how many DNA repeats cause a transition from a healthy to diseased state and the molecular mechanisms enabling rapid repeat expansion. This will be carried out with the overall aim of identifying genetic factors and/or therapeutic approaches that modulate C9orf72 instability.

Who or what inspired you to pursue your research interests?

I was initially drawn to study biochemistry because I found the idea that a single cell could contain the information to code an entire person absolutely astonishing. As I learnt more about the complexity within a cell, I became particularly fascinated by how highly accurate processes such as DNA replication and transcription must be coordinated with one another to maintain genome stability. When these intricate molecular pathways of coordination fail, genomic instability and disease can result. This is why I wanted to pursue a PhD investigating how genomic instability arises and how this can be prevented therapeutically.