ORCID Profile
0000-0002-4653-912X
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
DOI: 10.1038/S41598-018-24672-W
Abstract: Mitochondrial morphology is important for the function of this critical organelle and, accordingly, altered mitochondrial structure is exhibited in many pathologies. Imaging of mitochondria can therefore provide important information about disease presence and progression. However, mitochondrial imaging is currently limited by the availability of agents that have the capacity to image mitochondrial morphology in both live and fixed s les. This can be particularly problematic in clinical studies or large, multi-centre cohort studies, where tissue archiving by fixation is often more practical. We previously reported the synthesis of an iridium coordination complex [Ir( ppy ) 2 ( MeTzPyPhCN )] + where ppy is a cyclometalated 2-phenylpyridine and TzPyPhCN is the 5-(5-(4-cyanophen-1-yl)pyrid-2-yl)tetrazolate ligand and showed that this complex (herein referred to as IraZolve-Mito) has a high specificity for mitochondria in live cells. Here we demonstrate that IraZolve-Mito can also effectively stain mitochondria in both live and fixed tissue s les. The staining protocol proposed is versatile, providing a universal procedure for cell biologists and pathologists to visualise mitochondria.
Publisher: Public Library of Science (PLoS)
Date: 23-08-2016
Publisher: Wiley
Date: 06-2012
Publisher: Cold Spring Harbor Laboratory
Date: 12-2017
Abstract: The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B ( ARID5B ) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2–4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the ARID5B gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. ARID5B positively regulates the expression of TAL1 and its regulatory partners. ARID5B also activates the expression of the oncogene MYC . Importantly, ARID5B is required for the survival and growth of T-ALL cells , and forced expression of ARID5B in immature thymocytes results in thymus retention, differentiation arrest, radioresistance, and tumor formation in zebrafish. Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL, thereby contributing to T-cell leukemogenesis.
Publisher: Wiley
Date: 09-2016
Abstract: Live cell imaging can provide important information on cellular dynamics however, the full utilisation of this technology has been h ered by the limitations of imaging reagents. Metal-based complexes have the potential to overcome many of the issues common to many current imaging agents. The rhenium (I)-based complex fac-[Re(CO)3 (1,10-phenanthroline)(4-pyridyltetrazolate)], herein referred to as ReZolve-ER(™) , shows promise as a live cell imaging agent with rapid cell uptake, low cytotoxicity, resistance to photobleaching and compatibility with multicolour imaging. ReZolve-ER(™) localised to the nuclear membrane/endoplasmic reticulum (ER) and allowed the detection of exocytotic events at the plasma membrane. Thus, we present a new imaging agent for monitoring live cell events in real time, which is ideal for imaging either short- or long-time courses.
Publisher: Informa UK Limited
Date: 2013
DOI: 10.4161/INTV.23889
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6MB00242K
Abstract: Localisation of a neutral rhenium( i ) tricarbonyl phenanthroline species to regions of high polar lipid concentrations is demonstrated by Fourier transform infrared (FTIR) microspectroscopy.
Publisher: The Company of Biologists
Date: 09-09-2015
DOI: 10.1242/BIO.013979
Abstract: Autophagy is an intracellular recycling and degradation process, which is important for energy metabolism, lipid metabolism, physiological stress response and organism development. During Drosophila development, autophagy is up-regulated in fat body and midgut cells, to control metabolic function and to enable tissue remodelling. Atg9 is the only transmembrane protein involved in the core autophagy machinery and is thought to have a role in autophagosome formation. During Drosophila development, Atg9 co-located with Atg8 autophagosomes, Rab11 endosomes and L 1 endosomes-lysosomes. RNAi silencing of Atg9 reduced both the number and the size of autophagosomes during development and caused morphological changes to hisomes/autolysosomes. In control cells there was compartmentalised acidification corresponding to intraluminal Rab11/L -1 vesicles, but in Atg9 depleted cells there were no intraluminal vesicles and the acidification was not compartmentalised. We concluded that Atg9 is required to form intraluminal vesicles and for localised acidification within hisomes/autolysosomes, and consequently when depleted, reduced the capacity to degrade and remodel gut tissue during development.
Publisher: Cambridge University Press (CUP)
Date: 12-07-2017
DOI: 10.1017/S2040174417000496
Abstract: Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some ex les of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ . These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1039/C6MT00243A
Abstract: Optical epifluorescence microscopy was used in conjunction with X-ray fluorescence imaging to monitor the stability and intracellular distribution of the luminescent rhenium(i) complex fac-[Re(CO)
Publisher: Wiley
Date: 02-05-2018
Abstract: Coronary heart disease is one of the largest causes of death worldwide, making this a significant health care issue. A critical problem for the adult human heart is that it does not undergo effective repair in response to damage, leaving patients with a poor prognosis. Unlike the adult, fetal hearts have the ability to repair after myocardial damage. Using two-photon microscopy, we have visualised the morphological and metabolic changes following myocardial infarction in sheep fetuses, to characterise response to cardiac injury in a mammalian model. Following myocardial infarction, fetal hearts showed no significant increase in collagen deposition in the region of the infarction, when compared to either the surrounding tissue or shams. In contrast, metabolic activity (i. e. NAD(P)H and FAD) was significantly reduced in the region of myocardial infarction, when compared to either the surrounding tissue or sham hearts. For comparison, we also imaged two hearts from preadolescent sheep (sham and myocardial infarction) and showed highly ordered collagen deposition with decreased metabolic activity within the infarcted area. Therefore, two-photon imaging had the capacity to image both morphological and metabolic changes in response to myocardial infarction and showed differences in the response with age. Picture: Two-photon imaging of myocardial infarction (b and d) enabled the visualisation of increased collagen (blue Em=431 nm) and changes in other tissue autofluorescence (green Em=489-606 nm) in fetal (a and b) and preadolescent (c and d) hearts, compared to shams (a and c). The excitation wavelength was 840 nm. Scale bars: 10 μm.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JINORGBIO.2017.10.003
Abstract: In this work we have developed a series of highly emissive europium(III) and terbium(III) complexes tethered to either folic acid (FA) or methotrexate (MTX), with the aim of developing visual probes that enable the imaging of folate receptors in cancer cells. The synthesis, photophysical properties and cellular behaviour are reported for four new lanthanide Ln(III) complexes, where either FA or MTX are tethered to 1,4,7-tris(carbonylmethyl)-10-(4'-quinolineacetic acid, (7'-acetamido)-1',2'-dihydro-2'-oxo)-1,4,7,10-tetraazacyclododecane Ln(III) complex, and Ln(III)=Eu(III) or Tb(III) herein referred to as Eu-FA, Eu-MTX, Tb-FA or Tb-MTX. All four complexes were found to be sensitive to the presence of the folate receptor in a range of cell lines. The MTX conjugates showed different cellular specificity in an oral adenosquamous carcinoma cell line (CAL-27) compared with the analogous FA conjugates. This suggests that it is viable to explore differences in folate receptors using folate vs. anti-folate probes, with labels that have different emissive properties (e.g. Eu-FA vs. Tb-MTX). The MTX complexes were found to be the most cytotoxic, with Eu-MTX showing greater cytotoxicity than free MTX or the isostructural Tb-MTX. This suggested that there could be a synergistic effect on toxicity for the Eu(III) chelate and the MTX components of the complex.
Publisher: Wiley
Date: 14-09-2011
DOI: 10.1111/J.1365-2915.2010.00908.X
Abstract: The Australian saltmarsh mosquito, Aedes c torhynchus (Diptera: Culicidae), is a significant biting pest and disease vector and is the subject of an eradication programme in New Zealand (NZ), where it has been resident for more than 10 years. To better understand the ecology of this common and widespread pest, we studied egg longevity and hatching patterns in the laboratory. By regularly testing for the presence of viable embryos, we found that eggs may last more than 15 months when stored dry (13% viable at this time). Eggs display instalment hatching, with no more than 56% of a batch hatching upon first inundation. Further hatching may occur for at least six inundations and some unhatched eggs may remain viable even after this. Variation in hatching rates can be observed using different water types, with weaker hatching media stimulating lower hatching rates spread over more inundations. By applying average hatching rates to a non-linear model of natural egg attrition, we showed that egg batches exposed to three inundations should be exhausted (zero live eggs present) in approximately 11 months at the conditions tested here. These findings have implications for the current eradication programme for Ae. c torhynchus in NZ and for our understanding of the ecology of a widespread and common disease vector in Australia.
Publisher: American Chemical Society (ACS)
Date: 13-04-2017
DOI: 10.1021/ACS.JPROTEOME.6B01032
Abstract: The evolutionary conserved family of 14-3-3 proteins appears to have a role in integrating numerous intracellular pathways, including signal transduction, intracellular trafficking, and metabolism. However, little is known about how this interactive network might be affected by the direct abrogation of 14-3-3 function. The loss of Drosophila 14-3-3ε resulted in reduced survival of mutants during larval-to-adult transition, which is known to depend on an energy supply coming from the histolysis of fat body tissue. Here we report a differential proteomic analysis of larval fat body tissue at the onset of larval-to-adult transition, with the loss of 14-3-3ε resulting in the altered abundance of 16 proteins. These included proteins linked to protein biosynthesis, glycolysis, tricarboxylic acid cycle, and lipid metabolic pathways. The ecdysone receptor (EcR), which is responsible for initiating the larval-to-adult transition, colocalized with 14-3-3ε in wild-type fat body tissues. The altered protein abundance in 14-3-3ε mutant fat body tissue was associated with transcriptional deregulation of alcohol dehydrogenase, fat body protein 1, and lamin genes, which are known targets of the EcR. This study indicates that 14-3-3ε has a critical role in cellular metabolism involving either molecular crosstalk with the EcR or direct interaction with metabolic proteins.
Publisher: Elsevier BV
Date: 11-2018
Publisher: Public Library of Science (PLoS)
Date: 21-12-2010
Publisher: Wiley
Date: 28-11-2018
Abstract: The heart has high metabolic demand to maintain function. The primary source of energy supply to support correct contractile muscle function differs between a fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and lactate oxidation, whereas following birth, there is a shift towards a reliance on mitochondrial metabolism and fatty acid oxidation. This change in metabolic status is an adaptation to different fuel availability, oxygenation and growth patterns. In this study, we have employed 2-photon excitation fluorescence microscopy to define the relationship between two critical metabolic cofactors nicotinamide adenine dinucleotide(P)H and flavin adenine dinucleotide, effectively utilizing a redox ratio to differentiate between the metabolic status in fetal (proliferative) and adult (quiescent/hypertrophic) hearts. Two-photon imaging was also used to visually confirm the known increase in collagen deposition in the adult heart. The changes observed were consistent with a hypertrophic growth profile and greater availability of fatty acids in the adult heart, compared to the proliferative fetal heart. Two-photon excitation fluorescence microscopy is therefore a convenient imaging technology that enables the monitoring of striated muscle architecture and the metabolic status of heart tissue. This imaging technology can potentially be employed to visualize cardiac and other muscle pathologies.
Publisher: Wiley
Date: 07-08-2017
Abstract: A family of five neutral cyclometalated iridium(III) tetrazolato complexes and their methylated cationic analogues have been synthesised and characterised. The complexes are distinguished by variations of the substituents or degree of π conjugation on either the phenylpyridine or tetrazolato ligands. The photophysical properties of these species have been evaluated in organic and aqueous media, revealing predominantly a solvatochromic emission originating from mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. These emissions are characterised by typically long excited-state lifetimes (∼hundreds of ns), and quantum yields around 5-10 % in aqueous media. Methylation of the complexes caused a systematic red-shift of the emission profiles. The behaviour and the effects of the different complexes were then examined in cells. The neutral species localised mostly in the endoplasmic reticulum and lipid droplets, whereas the majority of the cationic complexes localised in the mitochondria. The amount of complexes found within cells does not depend on lipophilicity, which potentially suggests erse uptake mechanisms. Methylated analogues were found to be more cytotoxic compared to the neutral species, a behaviour that might to be linked to a combination of uptake and intracellular localisation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4RA00050A
Abstract: Neutral Re( i ) tetrazolato complexes exhibit labeling of lipid droplets with high specificity.
No related grants have been discovered for Christie Bader.