2012 - 2016 Ph.D. University of Sydney
Primary Supervisor: A/Prof. Geraldine O’Neill (University of Sydney; Australia)
Auxiliary Supervisor: Prof. Ben Fabry (Friedrich-Alexander Universität, Germany)
Thesis Title: Structural homology and functional similarity: Cas family proteins, NEDD9 and p130Cas, are functionally distinct focal adhesion molecules.
2008 Bachelor of Science (Honours). University of Wollongong
Supervisor: Dr Jason McArthur
2004 - 2007 Bachelor of Science. University of Wollongong
27
Scopus Publications
Scopus Publications
Cell fragmentation in mouse preimplantation embryos induced by ectopic activation of the polar body extrusion pathway Diane Pelzer, Ludmilla de Plater, Peta Bradbury, Adrien Eichmuller, Anne Bourdais, et al. EMBO Journal, 2023 Cell fragmentation is commonly observed in human preimplantation embryos and is associated with poor prognosis during assisted reproductive technology (ART) procedures. However, the mechanisms leading to cell fragmentation remain largely unknown. Here, light sheet microscopy imaging of mouse embryos reveals that inefficient chromosome separation due to spindle defects, caused by dysfunctional molecular motors Myo1c or dynein, leads to fragmentation during mitosis. Extended exposure of the cell cortex to chromosomes locally triggers actomyosin contractility and pinches off cell fragments. This process is reminiscent of meiosis, during which small GTPase‐mediated signals from chromosomes coordinate polar body extrusion (PBE) by actomyosin contraction. By interfering with the signals driving PBE, we find that this meiotic signaling pathway remains active during cleavage stages and is both required and sufficient to trigger fragmentation. Together, we find that fragmentation happens in mitosis after ectopic activation of actomyosin contractility by signals emanating from DNA, similar to those observed during meiosis. Our study uncovers the mechanisms underlying fragmentation in preimplantation embryos and, more generally, offers insight into the regulation of mitosis during the maternal‐zygotic transition.
Spatial reorganization of F-actin in respiratory cells as measured by Brillouin microscopy Hadi Mahmodi, Peta Bradbury, Aylin Cidem, H. X. Ong, Daniela Traini, et al. European Conference on Biomedical Optics Ecbo 2023, 2023 Brillouin microscopy has emerged as a non-invasive and label-free technique to map micro-mechanical properties of cells. Here we apply Brillouin microscopy to probe reorganization of F-actin network in respiratory cells treated with Timothy grass pollen protein extracts. The results of our measurements in conjunction with clustering data analysis confirm spatial cellular reorganization of F-actin proteins and compromised junctional integrity in treated cells as compared to controls.
Spatial reorganization of F-actin in respiratory cells as measured by Brillouin microscopy Hadi Mahmodi, Peta Bradbury, Aylin Cidem, H. X. Ong, Daniela Traini, et al. Proceedings of SPIE the International Society for Optical Engineering, 2023 Brillouin microscopy has emerged as a non-invasive and label-free technique to map micro-mechanical properties of cells. Here we apply Brillouin microscopy to probe reorganization of F-actin network in respiratory cells treated with Timothy grass pollen protein extracts. The results of our measurements in conjunction with clustering data analysis confirm spatial cellular reorganization of F-actin proteins and compromised junctional integrity in treated cells as compared to controls.
In vitro testing and efficacy of poly-lactic acid coating incorporating antibiotic loaded coralline bioceramic on Ti6Al4V implant against Staphylococcus aureus Ipek Karacan, Besim Ben‐Nissan, Jerran Santos, Stanley Yiu, Peta Bradbury, et al. Journal of Tissue Engineering and Regenerative Medicine, 2022 Biofilm formation on an implant surface is most commonly caused by the human pathogenic bacteria Staphylococcus aureus, which can lead to implant related infections and failure. It is a major problem for both implantable orthopedic and maxillofacial devices. The current antibiotic treatments are typically delivered orally or in an injectable form. They are not highly effective in preventing or removing biofilms, and they increase the risk of antibiotic resistance of bacteria and have a dose‐dependent negative biological effect on human cells. Our aim was to improve current treatments via a localized and controlled antibiotic delivery‐based implant coating system to deliver the antibiotic, gentamicin (Gm). The coating contains coral skeleton derived hydroxyapatite powders (HAp) that act as antibiotic carrier particles and have a biodegradable poly‐lactic acid (PLA) thin film matrix. The system is designed to prevent implant related infections while avoiding the deleterious effects of high concentration antibiotics in implants on local cells including primary human adipose derived stem cells (ADSCs). Testing undertaken in this study measured the rate of S. aureus biofilm formation and determined the growth rate and proliferation of ADSCs. After 24 h, S. aureus biofilm formation and the percentage of live cells found on the surfaces of all 5%–30% (w/w) PLA‐Gm‐(HAp‐Gm) coated Ti6Al4V implants was lower than the control samples. Furthermore, Ti6Al4V implants coated with up to 10% (w/w) PLA‐Gm‐(HAp‐Gm) did not have noticeable Gm related adverse effect on ADSCs, as assessed by morphological and surface attachment analyses. These results support the use and application of the antibacterial PLA‐Gm‐(HAp‐Gm) thin film coating design for implants, as an antibiotic release control mechanism to prevent implant‐related infections.
Testing 3D printed biological platform for advancing simulated microgravity and space mechanobiology research Giulia Silvani, Peta Bradbury, Carin Basirun, Christine Mehner, Detina Zalli, et al. Npj Microgravity, 2022 The advancement of microgravity simulators is helping many researchers better understanding the impact of the mechanically unloaded space environment on cellular function and disfunction. However, performing microgravity experiments on Earth, using simulators such as the Random Positioning Machine, introduces some unique practical challenges, including air bubble formation and leakage of growth medium from tissue culture flask and plates, all of which limit research progress. Here, we developed an easy-to-use hybrid biological platform designed with the precision of 3D printing technologies combined with PDMS microfluidic fabrication processes to facilitate reliable and reproducible microgravity cellular experiments. The system has been characterized for applications in the contest of brain cancer research by exposing glioblastoma and endothelial cells to 24 h of simulated microgravity condition to investigate the triggered mechanosensing pathways involved in cellular adaptation to the new environment. The platform demonstrated compatibility with different biological assays, i.e., proliferation, viability, morphology, protein expression and imaging of molecular structures, showing advantages over the conventional usage of culture flask. Our results indicated that both cell types are susceptible when the gravitational vector is disrupted, confirming the impact that microgravity has on both cancer and healthy cells functionality. In particular, we observed deactivation of Yap-1 molecule in glioblastoma cells and the remodeling of VE-Cadherin junctional protein in endothelial cells. The study provides support for the application of the proposed biological platform for advancing space mechanobiology research, also highlighting perspectives and strategies for developing next generation of brain cancer molecular therapies, including targeted drug delivery strategies.
Tropomyosin 2.1 collaborates with fibronectin to promote TGF-β1-induced contraction of human lung fibroblasts Peta Bradbury, Cassandra P. Nader, Aylin Cidem, Sandra Rutting, Dianne Sylvester, et al. Respiratory Research, 2021 Many lung diseases are characterized by fibrosis, leading to impaired tissue patency and reduced lung function. Development of fibrotic tissue depends on two-way interaction between the cells and the extra-cellular matrix (ECM). Concentration-dependent increased stiffening of the ECM is sensed by the cells, which in turn increases intracellular contraction and pulling on the matrix causing matrix reorganization and further stiffening. It is generally accepted that the inflammatory cytokine growth factor β1 (TGF-β1) is a major driver of lung fibrosis through the stimulation of ECM production. However, TGF-β1 also regulates the expression of members of the tropomyosin (Tm) family of actin associating proteins that mediate ECM reorganization through intracellular-generated forces. Thus, TGF-β1 may mediate the bi-directional signaling between cells and the ECM that promotes tissue fibrosis. Using combinations of cytokine stimulation, mRNA, protein profiling and cellular contractility assays with human lung fibroblasts, we show that concomitant induction of key Tm isoforms and ECM by TGF-β1, significantly accelerates fibrotic phenotypes. Knocking down Tpm2.1 reduces fibroblast-mediated collagen gel contraction. Collectively, the data suggest combined ECM secretion and actin cytoskeleton contractility primes the tissue for enhanced fibrosis. Our study suggests that Tms are at the nexus of inflammation and tissue stiffening. Small molecules targeting specific Tm isoforms have recently been designed; thus targeting Tpm2.1 may represent a novel therapeutic target in lung fibrosis.
A 3D-Bioprinted Vascularized Glioblastoma-on-a-Chip for Studying the Impact of Simulated Microgravity as a Novel Pre-Clinical Approach in Brain Tumor Therapy Giulia Silvani, Carin Basirun, Hanjie Wu, Christine Mehner, Kate Poole, et al. Advanced Therapeutics, 2021 Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors and urgently requires the development of new therapeutic strategies. In this study, an innovative hybrid in vitro vascularized GBM‐on‐a‐chip model is presented as a strategic integration of microfluidics and 3D bioprinting technologies. The system can recreate the compartmentalized brain tumor microenvironment, comprising the functional blood brain barrier (BBB) and the adjacent 3D perivascular tumor niche, by selectively mimicking physiological shear stress and cell–cell, cell–matrix mechanical interaction. The GBM‐on‐a‐chip model was evaluated under simulated microgravity (µG) condition as a form of mechanical unloading showing a significant cell morphological and mechanotransduction response thereby indicating that gravitational forces play an important role in glioblastoma mechanical regulation. The proposed GBM‐on‐a‐chip represents a meaningful biological tool for further research in cancer mechanobiology and pre‐clinical approach in brain tumor therapy.
How do mechanics guide fibroblast activity? Complex disruptions during emphysema shape cellular responses and limit research Mathew N. Leslie, Joshua Chou, Paul M. Young, Daniela Traini, Peta Bradbury, et al. Bioengineering, 2021 The emphysema death toll has steadily risen over recent decades, causing the disease to become the third most common cause of death worldwide in 2019. Emphysema is currently incurable and could be due to a genetic condition (Alpha-1 antitrypsin deficiency) or exposure to pollutants/irritants, such as cigarette smoke or poorly ventilated cooking fires. Despite the growing burden of emphysema, the mechanisms behind emphysematous pathogenesis and progression are not fully understood by the scientific literature. A key aspect of emphysematous progression is the destruction of the lung parenchyma extracellular matrix (ECM), causing a drastic shift in the mechanical properties of the lung (known as mechanobiology). The mechanical properties of the lung such as the stiffness of the parenchyma (measured as the elastic modulus) and the stretch forces required for inhalation and exhalation are both reduced in emphysema. Fibroblasts function to maintain the structural and mechanical integrity of the lung parenchyma, yet, in the context of emphysema, these fibroblasts appear incapable of repairing the ECM, allowing emphysema to progress. This relationship between the disturbances in the mechanical cues experienced by an emphysematous lung and fibroblast behaviour is constantly overlooked and consequently understudied, thus warranting further research. Interestingly, the failure of current research models to integrate the altered mechanical environment of an emphysematous lung may be limiting our understanding of emphysematous pathogenesis and progression, potentially disrupting the development of novel treatments. This review will focus on the significance of emphysematous lung mechanobiology to fibroblast activity and current research limitations by examining: (1) the impact of mechanical cues on fibroblast activity and the cell cycle, (2) the potential role of mechanical cues in the diminished activity of emphysematous fibroblasts and, finally, (3) the limitations of current emphysematous lung research models and treatments as a result of the overlooked emphysematous mechanical environment.
