Gary Morris is a Research Fellow at the Centre for Neuroscience and Regenerative Medicine in the Faculty of Science. After graduating from the University of Otago in 2009 (with a Bachelor of Science in Biochemistry) and in 2011 (with a Master of Science in Biochemistry), Gary joined Prof. Bryce Vissel’s group at the Garvan Institute of Medical Research to commence his PhD in 2012. His PhD project, completed at the University of New South Wales in 2017, focussed on the development of novel therapeutics in a preclinical model of stroke.
Gary’s current work investigates the cellular and molecular mechanisms of neurodegeneration in both Alzheimer’s disease and stroke. In particular he aims to understand the critical role played by synapses, microglia and astrocytes in health and disease.
- Neurodegenerative diseases – Alzheimers Disease, Stroke
- Glial cells - Microglia, Astrocytes, Oligodendrocytes
- Synaptic plasticity
Can supervise: YES
Rentsch, P, Stayte, S, Morris, GP & Vissel, B 2019, 'Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on l-Dopa induced dyskinesia', BMC NEUROSCIENCE, vol. 20.View/Download from: UTS OPUS or Publisher's site
Morris, GP, Clark, IA & Vissel, B 2018, 'Questions concerning the role of amyloid-beta in the definition, aetiology and diagnosis of Alzheimer's disease', ACTA NEUROPATHOLOGICA, vol. 136, no. 5, pp. 663-689.View/Download from: Publisher's site
Morris, GP, Wright, AL, Tan, RP, Gladbach, A, Ittner, LM & Vissel, B 2016, 'A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice.', PLoS ONE, vol. 11, no. 2, pp. 1-34.View/Download from: UTS OPUS or Publisher's site
The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method.
Morris, GP, Clark, IA & Vissel, B 2014, 'Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer's disease.', Acta Neuropathologica Communications, vol. 2, pp. 1-21.View/Download from: UTS OPUS or Publisher's site
The amyloid hypothesis has driven drug development strategies for Alzheimer's disease for over 20 years. We review why accumulation of amyloid-beta (A) oligomers is generally considered causal for synaptic loss and neurodegeneration in AD. We elaborate on and update arguments for and against the amyloid hypothesis with new data and interpretations, and consider why the amyloid hypothesis may be failing therapeutically. We note several unresolved issues in the field including the presence of A deposition in cognitively normal individuals, the weak correlation between plaque load and cognition, questions regarding the biochemical nature, presence and role of A oligomeric assemblies in vivo, the bias of pre-clinical AD models toward the amyloid hypothesis and the poorly explained pathological heterogeneity and comorbidities associated with AD. We also illustrate how extensive data cited in support of the amyloid hypothesis, including genetic links to disease, can be interpreted independently of a role for A in AD. We conclude it is essential to expand our view of pathogenesis beyond A and tau pathology and suggest several future directions for AD research, which we argue will be critical to understanding AD pathogenesis.
Morris, GP, Clark, IA, Zinn, R & Vissel, B 2013, 'Microglia: A new frontier for synaptic plasticity, learning and memory, and neurodegenerative disease research', NEUROBIOLOGY OF LEARNING AND MEMORY, vol. 105, pp. 40-53.View/Download from: UTS OPUS or Publisher's site
Ryan, MM, Morris, GP, Mockett, BG, Bourne, K, Abraham, WC, Tate, WP & Williams, JM 2013, 'Time-dependent changes in gene expression induced by secreted amyloid precursor protein-alpha in the rat hippocampus.', BMC Genomics, vol. 14, pp. 1-14.View/Download from: UTS OPUS or Publisher's site
BACKGROUND: Differential processing of the amyloid precursor protein liberates either amyloid-ß, a causative agent of Alzheimer's disease, or secreted amyloid precursor protein-alpha (sAPP), which promotes neuroprotection, neurotrophism, neurogenesis and synaptic plasticity. The underlying molecular mechanisms recruited by sAPP that underpin these considerable cellular effects are not well elucidated. As these effects are enduring, we hypothesised that regulation of gene expression may be of importance and examined temporally specific gene networks and pathways induced by sAPP in rat hippocampal organotypic slice cultures. Slices were exposed to 1 nM sAPP or phosphate buffered saline for 15 min, 2 h or 24 h and sAPP-associated gene expression profiles were produced for each time-point using Affymetrix Rat Gene 1.0 ST arrays (moderated t-test using Limma: p<0.05, and fold change±1.15). RESULTS: Treatment of organotypic hippocampal slice cultures with 1 nM sAPP induced temporally distinct gene expression profiles, including mRNA and microRNA associated with Alzheimer's disease. Having demonstrated that treatment with human recombinant sAPP was protective against N-methyl d-aspartate-induced toxicity, we next explored the sAPP-induced gene expression profiles. Ingenuity Pathway Analysis predicted that short-term exposure to sAPP elicited a multi-level transcriptional response, including upregulation of immediate early gene transcription factors (AP-1, Egr1), modulation of the chromatin environment, and apparent activation of the constitutive transcription factors CREB and NF-B. Importantly, dynamic regulation of NF-B appears to be integral to the transcriptional response across all time-points. In contrast, medium and long exposure to sAPP resulted in an overall downregulation of gene expression. While these results suggest commonality between sAPP and our previously reported analysis of plasticity-related gene expression, we found little crossover ...
Morris, GP, Wright, AL, Stayte, S, Zinn, R, Tan, RP & Vissel, B 2017, 'Attaining reliable data in pre-clinical mouse models of middle cerebral artery occlusion: a case study with brain-derived and glial-derived neurotrophic factors'.
Morris, GP, Wright, AL, Stayte, S, Zinn, R, Tan, RP & Vissel, B 2016, 'The neuroprotective capabilities of glial-derived neurotrophic factor following intraluminal filament middle cerebral artery occlusion in mice'.
Morris, GP, Ryan, MM, Bourne, K & Tate, WP 2011, 'Understanding how secreted amyloid precursor protein- (sAPP) signals changes in gene expression in neurons'.
Purpose: Secreted amyloid precursor protein- (sAPP), a 612 amino
acid brain protein, can be neurotrophic, neuroprotective and antiapoptotic.
The balance between sAPP and the toxic amyloid- peptide
(both processed from APP) may be critical to the disease process in
Alzheimers disease. RER, a peptide motif within sAPP is reported to
be capable of mimicking the functions of sAPP. In this study we validate
that sAPP changes gene expression, and determine whether the RER
motif can mimic these changes. Methods: The effects of sAPP on
three candidate genes, Insulin like growth factor-2 (IGF2), Insulin like
growth factor binding protein-2 (IGFBP2) and Seladin-1, were modeled
in cultured SHSY-5Y neuroblastoma (neuron-like) cells. Cells in triplicate
were treated with either saline, recombinant sAPP (2.5nM) or RER
(10 nM) from 30min to 24h. The relative levels of the transcripts were
determined in a SYBR Green quantitative PCR assay, where HPRT
was the normalizing control gene. Data are an average of two separate
experiments (n=6). Results: sAPP treatment resulted in a transient
increase in the expression of both IGF2 (5.5 fold, p<0.05), IGFBP2 (1.7
fold) and Seladin-1 (2.4 fold) after 30min but the increase in expression
was not sustained after 60min. At 24h there was a secondary increase in
expression of all three genes. RER peptide had similar but lower activity
(IGF2 at 30min, 2.3 fold) than sAPP. Conclusion: Both sAPP and
the RER motif as a peptide can induce gene expression changes in
undifferentiated neuroblastoma cells, and the motif may play an important role in the protective properties of sAPP in neurons.
Ryan, MM, Morris, GP, Bourne, K, Mockett, BG, Abraham, WC, Tate, WP & Williams, JM 2009, 'Regulation of gene expression by sAPP and RER derivative in differentiated neuroblastoma cells'.
The amyloid precursor protein (APP) is cleaved by two opposing pathways, the most well understood of which yields the neurotoxic peptide, amyloid-, while the second mutually exclusive pathway yields a secreted molecule, sAPP, a 612 amino acid peptide. Infusion of sAPP in vivo enhances the LTP-model of memory and inhibition of endogenous sAPP synthesis in vivo by infusion of TAPI, a metalloprotease inhibitor, results in a reduced retention of spatial memories. This effect, however, can be rescued by co-infusion of recombinant sAPP.