Neil O'Brien-Simpson

Prof. Neil O'Brien-Simpson

Oral Health CRC, Melbourne Dental School, 720 Swanston Street, The University of Melbourne, Carlton Victoria 3010, Australia
orcid

Research Focus & Metrics

Academic Career Length

30Years (1997-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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12 September 2016 in Nature Microbiology
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Journal Article
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SLShu J. Lam
Shu J. Lam
NONeil O'Brien-Simpson
Neil O'Brien-Simpson
NPNamfon Pantarat
Namfon Pantarat
ASAdrian Sulistio
Adrian Sulistio
EWEdgar Wong
Edgar Wong
GQGreg G. Qiao
Greg G. Qiao

4 November 2014 in Polymer Chemistry
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SLSean Lowe
Sean Lowe
NONeil O'Brien-Simpson
Neil O'Brien-Simpson
LCLuke A. Connal
Luke A. Connal
This review highlights antibiofouling polymer interfaces with emphasis on the latest developments using poly(ethylene glycol) and the design new polymeric structures.

12 March 2021 in Chemical Society Reviews
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Journal Article
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Wenyi LiWenyi Li
Wenyi Li
FSFrances Separovic
Frances Separovic
NONeil O'Brien-Simpson
Neil O'Brien-Simpson
JWJohn D. Wade
John D. Wade
Chemical modification of antimicrobial peptides augments their antibacterial action via multiple mechanisms.

3 October 2018 in PLOS ONE
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Open access
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VIVladimir Ilievski
Vladimir Ilievski
PZPaulina K Zuchowska
Paulina K Zuchowska
SGStefan J Green
Stefan J Green
PTPeter T Toth
Peter T Toth
MRMichael E Ragozzino
Michael E Ragozzino
KWKeiko Watanabe
Keiko Watanabe
The results from cross sectional and longitudinal studies show that periodontitis is closely associated with cognitive impairment (CI) and Alzhemer’s Disease (AD). Further, studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain. However, neuropathology resulting from Pg oral application is not known. In this work, we tested the hypothesis that repeated exposure of wild type C57BL/6 mice to orally administered Pg results in neuroinflammation, neurodegeneration, microgliosis, astrogliosis and formation of intra- and extracellular amyloid plaque and neurofibrillary tangles (NFTs) which are pathognomonic signs of AD. Experimental chronic periodontitis was induced in ten wild type 8-week old C57BL/6 WT mice by repeated oral application (MWF/week) of Pg/gingipain for 22 weeks (experimental group). Another 10 wild type 8-week old C57BL/6 mice received vehicle alone (control group) MWF per week for 22 weeks. Brain tissues were collected and the presence of Pg/gingipain was determined by immunofluorescence (IF) microscopy, confocal microscopy, and quantitative PCR (qPCR). The hippocampi were examined for the signs of neuropathology related to AD: TNFα, IL1β, and IL6 expression (neuroinflammation), NeuN and Fluoro Jade C staining (neurodegeneration) and amyloid beta1-42 (Aβ42) production and phosphorylation of tau protein at Ser396 were assessed by IF and confocal microscopy. Further, gene expression of amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), a disintegrin and metalloproteinase domain-containing protein10 (ADAM10) for α-secretase and presenilin1 (PSEN1) for ɣ-secretase, and NeuN (rbFox3) were determined by RT-qPCR. Microgliosis and astrogliosis were also determined by IF microscopy. Pg/gingipain was detected in the hippocampi of mice in the experimental group by immunohistochemistry, confocal microscopy, and qPCR confirming the translocation of orally applied Pg to the brain. Pg/gingipain was localized intra-nuclearly and peri-nuclearly in microglia (Iba1+), astrocytes (GFAP+), neurons (NeuN+) and was evident extracellularly. Significantly greater levels of expression of IL6, TNFα and IL1β were evident in experimental as compared to control group (p<0.01, p<0.00001, p<0.00001 respectively). In addition, microgliosis and astrogliosis were evident in the experimental but not in control group (p <0.01, p<0.0001 respectively). Neurodegeneration was evident in the experimental group based on a fewer number of intact neuronal cells assessed by NeuN positivity and rbFOX3 gene expression, and there was a greater number of degenerating neurons in the hippocampi of experimental mice assessed by Fluoro Jade C positivity. APP and BACE1 gene expression were increased in experimental group compared with control group (p<0.05, p<0.001 respectively). PSEN1 gene expression was higher in experimental than control group but the difference was not statistically significant (p = 0.07). ADAM10 gene expression was significantly decreased in experimental group compared with control group (p<0.01). Extracellular Aβ42 was detected in the parenchyma in the experimental but not in the control group (p< 0.00001). Finally, phospho-Tau (Ser396) protein was detected and NFTs were evident in experimental but not in the control group (p<0.00001). This study is the first to show neurodegeneration and the formation of extracellular Aβ42 in young adult WT mice after repeated oral application of Pg. The neuropathological features observed in this study strongly suggest that low grade chronic periodontal pathogen infection can result in the development of neuropathology that is consistent with that of AD.

23 June 2020 in Chemical Society Reviews
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AMAlicia Rasines Mazo
Alicia Rasines Mazo
SAStephanie Allison-Logan
Stephanie Allison-Logan
FKFatemeh Karimi
Fatemeh Karimi
NCNicholas Jun-An Chan
Nicholas Jun-An Chan
WQWenlian Qiu
Wenlian Qiu
GQGreg Guanghua Qiao
Greg Guanghua Qiao
Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.

20 November 2013 in ACS Nano
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Journal Article
Open access
YYYan Yan
Yan Yan
KGKatelyn T. Gause
Katelyn T. Gause
MKMarloes M. J. Kamphuis
Marloes M. J. Kamphuis
CAChing-Seng Ang
Ching-Seng Ang
NONeil O'Brien-Simpson
Neil O'Brien-Simpson
FCFrank Caruso
Frank Caruso
Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The protein corona can significantly influence particle–cell interactions, including internalization and pathway activation. In this work, we demonstrate the differential roles of a given protein corona formed in cell culture media in particle uptake by monocytes and macrophages. By exposing disulfide-stabilized poly(methacrylic acid) nanoporous polymer particles (PMASH NPPs) to complete cell growth media containing 10% fetal bovine serum, a protein corona, with the most abundant component being bovine serum albumin, was characterized. Upon adsorption onto the PMASH NPPs, native bovine serum albumin (BSA) was found to undergo conformational changes. The denatured BSA led to a significant decrease in internalization efficiency in human monocytic cells, THP-1, compared with the bare particles, due to reduced cell membrane adhesion. In contrast, the unfolded BSA on the NPPs triggered class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like cells (dTHP-1) without a significant impact on the overall internalization efficiency. Taken together, this work demonstrates the disparate effects of a given protein corona on particle–cell interactions, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities.