Finula is a postgraduate researcher based at the BMC, University of Sydney. She started laboratory research into MSA in 2018.
Finula is a postgraduate researcher based at the BMC, University of Sydney. She started laboratory research into MSA in 2018.
Forefront Group: Halliday Lab
Supervisors
A/Professor Scott Woojin Kim, Professor Glenda Halliday
Affiliate Organisations
Brain and Mind Centre, University of Sydney
Expertise:
Neurodegeneration of interest:
MSA, PD, Lipidopathy
Specific Skills:
Project - Functional Study of the Cadherin-4 Gene in Multiple System Atrophy
Disease area:
MSA
Research Project Aims
Research Project Description
Background:
MSA is a rare neurodegenerative disease of the central and autonomic nervous system. The neuropathological hallmark of MSA are glial cytoplasmic inclusions (GCI) within oligodendrocytes, the myelinating neural support cells. The inclusions are predominantly formed by misfolded α-synuclein, a small presynaptic protein which additionally encompasses Lewy bodies and Lewy neurites in neurons affected by Parkinson’s disease and related syndromes. However, MSA is distinguishable from Parkinson’s disease as an oligodendrogliopathy resulting in subsequent neuron death, indicating a separate pathogenic mechanism. This distinction warrants researching MSA neuropathogenesis in its own right. Incidentally, a genome wide association study (Sailer et al., 2016) identified a number of novel gene variants in an MSA cohort. These were the subject of recent investigation at the Halliday laboratory, with preliminary findings indicating alterations in CDH4 expression in MSA disease-affected tissue, and an impact of this protein on downstream MSA neuropathic genes in a cell model. It is vital to replicate and investigate this further to determine the role CDH4 may play in MSA neuropathogenesis.
Objectives & Methods:
This research will measure CDH4 gene and protein expression in MSA cohorts using sanger sequencing, quantitative polymerase chain reaction, protein fractionation and western blotting. The involvement of lipids in MSA and their relationship to CDH4 will be considered via lipidomics. We will additionally conduct CDH4 transfection of oligodendrocyte cells to investigate the impact on downstream MSA neuropathic genes and processes. Following this, we will decipher structural and functional features of CDH4 to determine the role it may play in MSA, and thus, its suitability as a therapeutic target or diagnostic biomarker.