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52. Enacting Remote and Flexible Learning Placements during a Global Pandemic—A Case Report.

Author

O'Brien, Siobhan

Abstract

The global pandemic significantly affected teacher training programs, specifically professional experience in schools. The past two years of teacher education have necessitated the innovation and adaption of traditional programs to ensure pre-service teachers' preparation and readiness to enter schools as graduates in Australia. This case report explores the creation and implementation of three innovations that were used to support pre-service teachers who undertook a remote and flexible learning placement due to school closures. The report presents the process implemented to best support the pre-service teachers and school mentors to deal with the disruption to professional experience caused. [ABSTRACT FROM AUTHOR]

Published
2023
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56. English and Literacies

Author

Ewing, Robyn, primary, O'Brien, Siobhan, additional, Rushton, Kathy, additional, Stewart, Lucy, additional, Burke, Rachel, additional, and Brosseuk, Deb, additional

Published
2022
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57. SCFFBXW7 regulates G2‐M progression through control of CCNL1 ubiquitination.

Author

O'Brien, Siobhan, Kelso, Susan, Steinhart, Zachary, Orlicky, Stephen, Mis, Monika, Kim, Yunhye, Lin, Sichun, Sicheri, Frank, and Angers, Stephane

Abstract

FBXW7, which encodes a substrate‐specific receptor of an SCF E3 ligase complex, is a frequently mutated human tumor suppressor gene known to regulate the post‐translational stability of various proteins involved in cellular proliferation. Here, using genome‐wide CRISPR screens, we report a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and describe CCNL1 as a new substrate of the SCF‐FBXW7 E3 ligase. Further analysis showed that the CCNL1–CDK11 complex is critical at the G2‐M phase of the cell cycle since defective CCNL1 accumulation, resulting from FBXW7 mutation, leads to shorter mitotic time. Cells harboring FBXW7 loss‐of‐function mutations are hypersensitive to treatment with a CDK11 inhibitor, highlighting a genetic vulnerability that could be leveraged for cancer treatment. Synopsis: The candidate oncogene CCNL1 is regulated by FBXW7 through ubiquitination and degradation in a Cul1‐dependent manner. FBXW7‐mutant cells depend on CCNL1 for growth, sensitizing them to OTS964, an inhibitor of CCNL1 kinase partner CDK11. FBXW7‐mutant cells depend on CCNL1 for growth.CCNL1 is a novel substrate of FBXW7.CCNL1 mediates mitotic progression and reliance on this signalling axis sensitizes cells to CDK11 inhibitor OTS964. [ABSTRACT FROM AUTHOR]

Published
2022
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66. Flexible surface electrodes targeting biopotential signals from forearm muscles for control of prosthetic hands: Part 2 - Characterization of substrates for strain sensors

Author

O'Brien, Siobhan, Searle, Thomas, Alici, Gursel, O'Brien, Siobhan, Searle, Thomas, and Alici, Gursel

Abstract

This study investigates the use of stretchable strain sensors as an alternative to the gold standard Ag/AgCl surface electromyography (sEMG) electrodes currently utilised to identify movement intention from a user during common hand gestures. Further building on the research in the companion paper, this study documents a series of strain characterisation experiments undertaken on three conductive textiles, two commercial conductive elastomers and one E-skin elastomer produced on site to determine the linearity of each sensor, along with the magnitude of hysteresis in a single stretch and release cycle, and any creep effects present. Gesture identification testing was performed in vivo on two participants, with the three most effective materials across five hand gestures, to assess the functionality of the materials as biopotential electrodes. For this series of experiments, the electrodes were positioned over the site of greatest strain for each gesture. Using a threshold-crossing paradigm, results demonstrated that a commercially sourced conductive fabric can identify 85% of hand gestures performed. The incorporation of flexible strain sensors in hand prosthetic control systems may further increase functionality of such devices, consequently boosting the quality of life of amputees.

Published
2019

67. Flexible surface electrodes targeting biopotential signals from forearm muscles for control of prosthetic hands: Part 1 - Characterisation of semg electrodes

Author

O'Brien, Siobhan, Searle, Thomas, Alici, Gursel, O'Brien, Siobhan, Searle, Thomas, and Alici, Gursel

Abstract

This study is Part 1 of two studies which investigate the use of various flexible surface sensors as an alternative to the gold standard Ag/AgCl surface electromyography (sEMG) electrodes in identifying movement intention from a user during common hand gestures. Three conductive textiles, two commercial conductive elastomers and one E-skin elastomer produced on site were tested as biopotential electrodes to establish the efficacy of each in gathering movement intention from the human brain at the level of the muscle. Testing was performed in vivo on two participants across three hand gestures, with results demonstrating that sEMG electrodes made from a commercially sourced conductive fabric can outperform the traditional Ag/AgCl sEMG electrodes, obtaining substantially larger peak and RMS measurements. Given the disadvantages of Ag/AgCl electrodes over long usage periods, namely their tendency to dry out and significant skin preparation, resulting in variable impedances and skin irritation respectively, the incorporation of flexible surface EMG electrodes in hand prosthetic control systems would increase functionality of the prosthetic devices, consequently increasing the quality of life of prosthetic hand users.

Published
2019

68. Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice

Author

Tao, Yuyong, primary, Mis, Monika, additional, Blazer, Levi, additional, Ustav, Mart, additional, Steinhart, Zachary, additional, Chidiac, Rony, additional, Kubarakos, Elli, additional, O'Brien, Siobhan, additional, Wang, Xiaomei, additional, Jarvik, Nick, additional, Patel, Nish, additional, Adams, Jarrett, additional, Moffat, Jason, additional, Angers, Stephane, additional, and Sidhu, Sachdev S, additional

Published
2019
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73. Author response: Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice

Author

Tao, Yuyong, primary, Mis, Monika, additional, Blazer, Levi, additional, Ustav, Mart, additional, Steinhart, Zachary, additional, Chidiac, Rony, additional, Kubarakos, Elli, additional, O'Brien, Siobhan, additional, Wang, Xiaomei, additional, Jarvik, Nick, additional, Patel, Nish, additional, Adams, Jarrett, additional, Moffat, Jason, additional, Angers, Stephane, additional, and Sidhu, Sachdev S, additional

Published
2019
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75. Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation.

Author

Barter, Matt J, Cheung, Kathleen, Falk, Julia, Panagiotopoulos, Andreas C, Cosimini, Caitlin, O'Brien, Siobhan, Teja-Putri, Karina, Neill, Graham, Deehan, David J, and Young, David A.

Subjects
CHROMATIN, INTERLEUKIN-1, DNA modification & restriction, GENE expression, TRANSCRIPTION factors, GENOME editing
Abstract

Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding. Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA, in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed. Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions that became more accessible following stimulation in the genes MMP13, IKBKE and C1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model. Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling. [ABSTRACT FROM AUTHOR]

Published
2021
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76. IPO11 mediates βcatenin nuclear import in a subset of colorectal cancers.

Author

Mis, Monika, O'Brien, Siobhan, Steinhart, Zachary, Sichun Lin, Hart, Traver, Moffat, Jason, and Angers, Stephane

Subjects
*COLORECTAL cancer, *NUCLEAR proteins, *CATENINS, *GENETIC regulation, *WNT signal transduction, *NUCLEOCYTOPLASMIC interactions
Abstract

Activation of Wnt signaling entails βcatenin protein stabilization and translocation to the nucleus to regulate context-specific transcriptional programs. The majority of colorectal cancers (CRCs) initiate following APC mutations, resulting in Wnt ligand-independent stabilization and nuclear accumulation of βcatenin. The mechanisms underlying βcatenin nucleocytoplasmic shuttling remain incompletely defined. Using a novel, positive selection, functional genomic strategy, DEADPOOL, we performed a genome-wide CRISPR screen and identified IPO11 as a required factor for βcatenin-mediated transcription in APC mutant CRC cells. IPO11 (Importin-11) is a nuclear import protein that shuttles cargo from the cytoplasm to the nucleus. IPO11-/- cells exhibit reduced nuclear βcatenin protein levels and decreased βcatenin target gene activation, suggesting IPO11 facilitates βcatenin nuclear import. IPO11 knockout decreased colony formation of CRC cell lines and decreased proliferation of patient-derived CRC organoids. Our findings uncover a novel nuclear import mechanism for βcatenin in cells with high Wnt activity. [ABSTRACT FROM AUTHOR]

Published
2020
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77. Court Of Appeal Outlines Key Principles On Suspending Employees With And Without Pay

Author

O'Brien, Siobhan

Subjects
Labor contracts -- Cases, Employment terminations -- Cases, Punitive damages -- Cases, Agricultural equipment industry -- Cases, Breach of trust -- Cases, Company legal issue, Business, international
Abstract

In Filice v. Complex Services, the Ontario Court of Appeal provided valuable guidance regarding constructive dismissal, investigative suspensions of employees without pay and proper damages assessments. The plaintiff/respondent in appeal [...]

Published
2018

78. Secondary messenger signalling influences Pseudomonas aeruginosaadaptation to sinus and lung environments

Author

Ruhluel, Dilem, Fisher, Lewis, Barton, Thomas E, Leighton, Hollie, Kumar, Sumit, Amores Morillo, Paula, O’Brien, Siobhan, Fothergill, Joanne L, and Neill, Daniel R

Abstract

Pseudomonas aeruginosais a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosaPAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments—sinus and lungs, under CF and non-CF conditions—selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivomodel. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes.Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifAand dipAphosphodiesterase genes and activating mutations in the siaAphosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.Graphical Abstract

Published
2024
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88. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma

Author

Cohen, E Suzanne, primary, Dobson, Claire L, additional, Käck, Helena, additional, Wang, Bing, additional, Sims, Dorothy A, additional, Lloyd, Christopher O, additional, England, Elizabeth, additional, Rees, D Gareth, additional, Guo, Hongwei, additional, Karagiannis, Sophia N, additional, O’Brien, Siobhan, additional, Persdotter, Sofia, additional, Ekdahl, Helena, additional, Butler, Robin, additional, Keyes, Feenagh, additional, Oakley, Sarah, additional, Carlsson, Mats, additional, Briend, Emmanuel, additional, Wilkinson, Trevor, additional, Anderson, Ian K, additional, Monk, Phillip D, additional, von Wachenfeldt, Karin, additional, Eriksson, Per-Olof F, additional, Gould, Hannah J, additional, Vaughan, Tristan J, additional, and May, Richard D, additional

Published
2014
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89. Humanization of Monoclonal Antibodies by CDR Grafting

Author

O'brien Siobhan and Jones Tarran

Subjects
Cloning, biology, Antigen, Chemistry, medicine.drug_class, Electroporation, Cdr grafting, medicine, biology.protein, Transfection, Antibody, Monoclonal antibody, Virology
Published
2003

91. The ultimate alternative : a single case study understanding Jason's journey from addiction to self-recovery

Author

Rich, Marcia, Grant Kalischuk, Ruth, O'Brien, Siobhan, Rich, Marcia, Grant Kalischuk, Ruth, and O'Brien, Siobhan

Abstract

The purpose of this research was to understand the lived experience of a person with a substance addiction that uses or has used alternative therapies for treatment. A single-case study approach was used to understand the lived experiences of Jason, a male in his mid-forties who is healing from a substance addiction. Through in-person interviewing and reading personal manuscripts written by the participant, data were collected. The data were analysed and interpreted using phenomenological and integral hermeneutics. Through the interpretations, it was clear that a major contributing factor to Jason’s drug use was the negative experiences he was carrying from his past. Once he was able to let go of the negativity and let his higher power guide him, his healing journey took a positive turn. Today, Jason lives in the moment and does not need drugs to heal the hurt he is feeling inside. He uses his ultimate alternative method, derived from within himself, to guide his journey in recovery.

Published
2012

92. Structural and Pharmacological Characterization of Novel Potent and Selective Monoclonal Antibody Antagonists of Glucose-dependent Insulinotropic Polypeptide Receptor

Author

Ravn, Peter, primary, Madhurantakam, Chaithanya, additional, Kunze, Susan, additional, Matthews, Evelyn, additional, Priest, Claire, additional, O'Brien, Siobhan, additional, Collinson, Andie, additional, Papworth, Monika, additional, Fritsch-Fredin, Maria, additional, Jermutus, Lutz, additional, Benthem, Lambertus, additional, Gruetter, Markus, additional, and Jackson, Ronald H., additional

Published
2013
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97. Hello Darling!: The Jeanne Little Story

Author

O'Brien, Siobhan and O'Brien, Siobhan

Abstract

The definitive biography of one of Australia's best loved stars of stage and screen, the fabulous and inimitable Jeanne Little.'He seemed to wince every time I opened my mouth. I thought I was getting somewhere until the day the professor's secretary told me he'd shot himself.'- Jeanne Little on her one brush with elocution lessons.The unmistakeable and inimitable Jeanne Little she of the amazing eyelashes and fabulous, if somewhat startling, dress sense (remember the green garbage bag frock?) is one of Australia's most loved and best known show business celebrities.A zany comedian with the voice of a truck driver, Jeanne got her start as a guest on the'Mike Walsh Show'in 1974 and never looked back. For over a decade she was the queen of Australian daytime television and beyond. With her distinctive presence, off-beat humour and flair for the innovative and unusual, Jeanne Little is an extraordinary woman. From Gold Logies to the Order of Australia to the hearts of Australian television and cabaret audiences alike, Jeanne wins them all. There's no one else quite like her. Here for the first time, along with revealing accounts of what really went on behind the craziness of Jeanne's seemingly accidental success, is the story of her remarkable childhood and her sometimes turbulent, often controversial but never dull life. Hilarious, heart-warming and moving, with dollops of Jeanne's own unique glamour and distinctive style, this is an engrossing biography of one of the true living treasures of the Australian stage and screen.

Published
2006

99. Humanization of Monoclonal Antibodies by CDR Grafting.

Author

Walker, John M., Welschof, Martin, Krauss, Jürgen, O'Brien, Siobhan, and Jones, Tarran

Abstract

The discovery of the process for making rodent monoclonal antibodies (MAbs) 26 years ago by Kohler and Milstein has led to a revolution in the treatment of over 50 major diseases, and has borne an industry whose products today represent 6% of total biotechnology sales. The full potential of this industry has still to be reached. [ABSTRACT FROM AUTHOR]

Published
2003
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