A5008169043- Amyotrophic Lateral Sclerosis Research
- Heat shock proteins research
- Prion Diseases and Protein Misfolding
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Cholinesterase and Neurodegenerative Diseases
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Schizophrenia research and treatment
- Cellular transport and secretion
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Receptor Mechanisms and Signaling
- Biochemical effects in animals
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Heterotopic Ossification and Related Conditions
- Medical Imaging and Pathology Studies
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Fungal and yeast genetics research
- Nuclear Structure and Function
The University of Queensland
2019-2025
The University of Sydney
2025
Park Centre for Mental Health
2023
University of Wollongong
2016-2021
Macquarie University
2019-2021
Illawarra Health and Medical Research Institute
2016-2021
University College London
2019
National Hospital for Neurology and Neurosurgery
2019
Abstract Aggregation of the RNA-binding protein, TDP-43, is unifying hallmark amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43-related neurodegeneration involves multiple changes to normal physiological which undergoes nuclear depletion, cytoplasmic mislocalisation, post-translational modification, aberrant liquid–liquid phase separation, preceding inclusion formation. Along with toxic aggregation, concurrent depletion dysfunction TDP-43 in cells pathology likely a key...
Abstract Understanding the mechanisms that drive TDP-43 pathology is integral to combating amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases. Here we generated a longitudinal quantitative proteomic map of cortex from cytoplasmic rNLS8 mouse model ALS FTLD, developed complementary open-access webtool, TDP-map ( https://shiny.rcc.uq.edu.au/TDP-map/ ). We identified distinct protein subsets enriched for diverse biological pathways...
TAR DNA binding protein 43 (TDP-43) pathology is a key feature of over 95% amyotrophic lateral sclerosis (ALS) and nearly half frontotemporal dementia (FTD) cases. The pathogenic mechanisms TDP-43 dysfunction are poorly understood, however, activation cell stress pathways may contribute to pathogenesis. We, therefore, sought identify which components critical for driving disease onset neurodegeneration in ALS FTD. We studied the rNLS8 transgenic mouse model, expresses human with...
Extra-motor symptoms are increasingly recognised in amyotrophic lateral sclerosis (ALS), encompassing cognitive, social, and behavioural deficits that can substantially impact quality of life. TAR DNA binding protein 43 (TDP-43) pathology is the central disease marker almost all cases ALS approximately half frontotemporal dementia (FTD). However, mechanisms linking TDP-43 with extra-motor TDP-43-associated neurodegenerative diseases remain unresolved. In this study, we used rNLS8 mouse...
Abstract Proteinaceous cytoplasmic inclusions are an indicator of dysfunction in normal cellular proteostasis and a hallmark many neurodegenerative diseases. We describe simple rapid new flow cytometry-based method to enumerate, characterise and, if desired, physically recover protein from cells. This technique can analyse resolve broad variety differing both size composition, making it applicable essentially any model intracellular aggregation. The also allows quantification the nuclear...
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living ALS, and its precise mechanisms action remain unclear. Most ALS cases are characterised by accumulation cytoplasmic TAR DNA binding protein 43 kDa (TDP‐43), understanding the effects in models closely recapitulate TDP‐43 pathology provide...
Protein aggregates that result in inclusion formation are a pathological hallmark common to many neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. Under conditions of cellular stress, activation the heat shock response (HSR) results an increase levels molecular chaperones is first line defence against formation. It remains be established whether disease-associated proteins inclusions themselves capable inducing HSR neuronal...
Preferential neuronal vulnerability is characteristic of several neurodegenerative diseases including the motor neuron disease amyotrophic lateral sclerosis (ALS). It well established that glia play a critical role in ALS, but it unknown whether regional differences ability to support neurons contribute specific pattern degeneration. In this study, using primary mixed glial cultures from different mouse CNS regions (spinal cord and cortex), we examined exist key pathways to, or protect...
Abstract Heat shock proteins (Hsps) are molecular chaperones that prevent the aggregation of client by facilitating their refolding, or trafficking them for degradation. The chaperone activities Hsps dependent on dynamic protein-protein interactions, including oligomerisation into large multi-subunit complexes. Thus, tagging with fluorescent can interfere activity. To overcome this limitation, we have exploited bicistronic constructs concurrent expression a non-tagged Hsp and reporter from...
Heterogeneity of glia in different CNS regions may contribute to the selective vulnerability neuronal populations neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS). Here, we explored regional variations expression heat shock protein 25 under acute and chronic stress. Hsp27 (Hsp27; murine orthologue: Hsp25) fulfils a number cytoprotective functions therefore be possible therapeutic target ALS. We identified subpopulation astrocytes primary mixed glial cultures that...
Abstract Protein aggregation that results in the formation of inclusions is strongly correlated with neuronal death and a pathological hallmark common to many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) Huntington’s disease. Cells are thought dramatically up-regulate levels heat shock proteins during periods cellular stress via induction response (HSR). Heat well-characterised molecular chaperones interact aggregation-prone either stabilise, refold, or traffic...
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living ALS and its precise mechanisms action remain unclear. Most cases are characterised by accumulation cytoplasmic TAR DNA binding protein 43 kDa (TDP-43), understanding the effects in models closely recapitulate TDP-43 pathology provide insights...
Abstract Understanding the mechanisms that drive TDP-43 pathology is integral to combating neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To address this, we sought determine timeline of proteomic alterations across disease course in proteinopathy. Using longitudinal quantitative proteomics analysis cortex samples from cytoplasmic rNLS8 mouse model ALS FTLD, identified several distinct protein subsets characterized by...
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping early-career researchers promote themselves alongside their papers. Rebecca San Gil author on ‘Neurodegenerative disease-associated protein aggregates are poor inducers heat shock response neuronal cells’, JCS. conducted research described this article while PhD student Heath Ecroyd's lab at Illawarra Health and Medical Research Institute, University Wollongong,...
Abstract TAR DNA binding protein 43 (TDP-43) pathology is a key feature of over 95% amyotrophic lateral sclerosis (ALS) and nearly half frontotemporal dementia (FTD) cases. The pathogenic mechanisms TDP-43 dysfunction are poorly understood, however activation cell stress pathways may contribute to pathogenesis. We therefore sought identify which components critical for driving disease onset neurodegeneration in ALS/FTD. studied the rNLS8 transgenic mouse model, expresses human with...
Abstract Dysfunction and aggregation of the RNA-binding protein, TDP-43, is unifying hallmark amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). Mechanisms relative contributions concurrent TDP-43 nuclear depletion, cytoplasmic accumulation, post-translational modification to neurodegeneration remain unresolved. We employed CRISPR/Cas9-mediated fluorescent tagging investigate how disease-associated stressors pathological alter abundance, localisation, self-assembly,...