Sharlynn Wu

Sharlynn was awarded a Bachelor of Science (Advanced) double majoring in Psychology and Molecular Biology and Genetics from The University of Sydney in 2016. The following year, they investigated the role of Hedgehog-related genes in neuronal development in Caenorhabditis elegans under the supervision of Dr Hannah Nicholas at The University of Sydney and was awarded a first-class Honours. In 2018, Sharlynn began a Master of Research with Prof Ian Blair at the Macquarie University Centre for Motor Neuron Disease Research and under the supervision of Dr Shu Yang. During the program, Sharlynn performed in vitro assays to determine the potential pathogenicity of ALS candidate variants. Under the guidance of associate supervisor Dr Albert Lee, Sharlynn also dabbled in proteomics to investigate whether any neurodegeneration-related pathways are affected by these candidate variants. Sharlynn is currently a PhD candidate they will continue to elucidate the pathogenicity of ALS candidate variants.

Forefront Group: Macquarie University Centre for Motor Neuron Disease Research


Dr Shu Yang (Principal), Dr Jennifer Fifita, Dr Alison Hogan, Dr Ian Blair


  • Cell biology
  • Molecular biology and genetics
  • Neuropathology

Affiliate Organisations

Macquarie University Centre for Motor Neuron Disease Research

Neurodegeneration of interest:


Specific Skills:

  • Molecular geneticist
  • Cell biologist
  • Immunofluorescence imaging
  • Gene regulation in C. elegans
  • Neuropathology
  • Protein fractionation
  • Western blotter
  • Proteomics analysis

Project - Elucidating the cellular mechanisms associated with novel and known ALS genes (2019 – 2022)

Research Project Abstract

Our group has developed a novel multidisciplinary gene discovery strategy that begins with whole genome and exome sequencing data of families with familial ALS (FALS). The strategy incorporates bioinformatics, in silico and in vitro methods that rank and prioritise candidate variants based on ALS-associated phenotypes. Interestingly, the genomic proximity of two out of five candidate variants suggested that they are likely co-inherited, which potentially produces oligogenic disease effects. Oligogenic inheritance refers to when two or more gene mutations are required for pathogenicity and has previously been implicated in ALS. Thus, this project seeks to determine the potential compound effect of both candidate variants on disease pathogenicity. I also aim to investigate the impact of intermediate polyglutamine expansions in the ALS-associated gene ATXN2 on FALS.

Disease area:


Research Project Description

  • In vitro prioritisation arm of our gene discovery strategy will be employed to investigate the potential oligogenicity of two candidate genes from a FALS family.
    • A bicistronic vector was designed and generated for expression in mammalian cell culture models. Following validation, this may serve as a platform for future oligogenic studies and will be used in the in vitro prioritisation arm of our novel multidisciplinary gene discovery strategy. This includes assays that assess toxicity, alterations to protein solubility and interaction with TDP-43 in human cell culture models.
    • We also have access to patient fibroblast cell lines, which will be characterised for ALS-associated phenotypes.
  • In vivo prioritisation arm of our gene discovery strategy involves the use of zebrafish (Danio rerio).
    • Transient and transgenic zebrafish models will be generated via mRNA microinjections and CRISPR-cas9. The resultant transgenic animals will be assessed using established behavioural assays to characterise motor function, such as swimming assays. Histopathological studies will also be performed to characterise neuropathological phenotypes.
  • Intermediate polyglutamine expansions in ATXN2
    • Frequency of intermediate expansions in the Australian cohort is determined via fragment analysis