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Sophie Farrow

BSc (Hons), PhD


Senior Postdoctoral Research Scientist

Parkinson's UK Senior Research Fellow

Research Summary

My research focuses on integrating multiple approaches to understand how we can utilise genetic information to better understand and treat people with sporadic Parkinson's disease. My current project focuses on prioritising gene targets for Parkinson's disease:

Parkinson’s disease (PD) is often described as an idiopathic disorder, indicating that the precise causes remain unknown. This lack of understanding surrounding the cause(s) of PD has led to a reliance on clinical presentation for diagnosis and treatment development. Despite being labelled idiopathic, a number of studies have identified genetic variants associated with an increased risk of sporadic PD, implicating potential molecular underpinnings that drive disease onset and pathogenesis. Consequently, exploring how and why these disease-associated genetic variants increase disease risk will provide insight into the potential causes of PD.

In this project I will use an integrative approach to combine basic cellular analyses with patient-derived datasets with the aim to enhance our fundamental molecular understanding of PD. This project is nested within the extensive Oxford Parkinson’s Disease Centre (OPDC) Discovery cohort, enabling access to bio-samples from a large number of people with Parkinson’s and RBD. Using these samples, I will generate multi-omic datasets derived from people with sporadic Parkinson’s and integrate these within the Priority Index pipeline. Specifically, I will generate chromatin profiles (Micro-C and ATACseq) of dopaminergic neurons and microglial cell lines derived from people with Parkinson’s. These datasets are crucial for identifying spatially-constrained target genes at PD-associated risk loci. To further refine the target genes, I will use genetic annotations and predictors and protein interaction networks, resulting in a list of potential drug-gene targets for PD. Subsequently, I will use RNAseq to determine the expression patterns of these prioritised genes in various samples (i.e., whole blood, cerebrospinal fluid) from people with Parkinson’s, compared to healthy controls. This genetic-driven approach will aim to inform our fundamental molecular understanding of PD and accelerate early-stage molecular-based drug selection and repurposing. 

Biography

I received my PhD from the University of Auckland (NZ) in 2022, where I studied the role of non-coding variants in Parkinson's disease. I then continued as a post-doctoral fellow within the same institute, on a project funded by the Michael J Fox Foundation, focusing predominantly on assigning function to non-coding variants associated with PD. This project combined a number of different molecular techniques including precise CRISPR editing, iPSC culture and differentiation, and RNAseq. Aside from my work with Parkinson's disease, I was also involved in the first phase of establishing a Newborn genomics platform for rare diseases in New Zealand. Upon my return to the UK, I was awarded a Parkinson's UK Senior Research Fellowship to begin developing my own independent research project and group (https://www.parkinsons.org.uk/news/awarding-nearly-ps600000-support-next-leaders-parkinsons-research).