School of BioSciences - Research Publications

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    Editorial: Salinity tolerance: From model or wild plants to adapted crops.
    Qiu, Q-S ; Melino, VJ ; Zhao, Z ; Qi, Z ; Sweetman, C ; Roessner, U (Frontiers Media SA, 2022)
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    Biochemical Changes in Two Barley Genotypes Inoculated With a Beneficial Fungus Trichoderma harzianum Rifai T-22 Grown in Saline Soil.
    Gupta, SVK ; Smith, PMC ; Natera, SHA ; Roessner, U (Frontiers Media SA, 2022)
    One of the most important environmental factors impacting crop plant productivity is soil salinity. Fungal endophytes have been characterised as biocontrol agents that help in plant productivity and induce resistance responses to several abiotic stresses, including salinity. In the salt-tolerant cereal crop barley (Hordeum vulgare L.), there is limited information about the metabolites and lipids that change in response to inoculation with fungal endophytes in saline conditions. In this study, gas chromatography coupled to mass spectrometry (GC-MS) and LC-electrospray ionisation (ESI)-quadrupole-quadrupole time of flight (QqTOF)-MS were used to determine the metabolite and lipid changes in two fungal inoculated barley genotypes with differing tolerance levels to saline conditions. The more salt-tolerant cultivar was Vlamingh and less salt tolerant was Gairdner. Trichoderma harzianum strain T-22 was used to treat these plants grown in soil under control and saline (200 mM NaCl) conditions. For both genotypes, fungus-colonised plants exposed to NaCl had greater root and shoot biomass, and better chlorophyll content than non-colonised plants, with colonised-Vlamingh performing better than uninoculated control plants. The metabolome dataset using GC-MS consisted of a total of 93 metabolites of which 74 were identified in roots of both barley genotypes as organic acids, sugars, sugar acids, sugar alcohols, amino acids, amines, and a small number of fatty acids. LC-QqTOF-MS analysis resulted in the detection of 186 lipid molecular species, classified into three major lipid classes-glycerophospholipids, glycerolipids, and sphingolipids, from roots of both genotypes. In Cultivar Vlamingh both metabolites and lipids increased with fungus and salt treatment while in Gairdner they decreased. The results from this study suggest that the metabolic pathways by which the fungus imparts salt tolerance is different for the different genotypes.
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    Measures of insulin sensitivity, leptin, and adiponectin concentrations in cats in diabetic remission compared to healthy control cats
    Gottlieb, S ; Rand, JS ; Ishioka, K ; Dias, DA ; Boughton, BA ; Roessner, U ; Ramadan, Z ; Anderson, ST (FRONTIERS MEDIA SA, 2022-07-29)
    Objectives: Firstly, to compare differences in insulin, adiponectin, leptin, and measures of insulin sensitivity between diabetic cats in remission and healthy control cats, and determine whether these are predictors of diabetic relapse. Secondly, to determine if these hormones are associated with serum metabolites known to differ between groups. Thirdly, if any of the hormonal or identified metabolites are associated with measures of insulin sensitivity. Animals: Twenty cats in diabetic remission for a median of 101 days, and 21 healthy matched control cats. Methods: A casual blood glucose measured on admission to the clinic. Following a 24 h fast, a fasted blood glucose was measured, and blood sample taken for hormone (i.e., insulin, leptin, and adiponectin) and untargeted metabolomic (GC-MS and LC-MS) analysis. A simplified IVGGT (1 g glucose/kg) was performed 3 h later. Cats were monitored for diabetes relapse for at least 9 months (270 days). Results: Cats in diabetic remission had significantly higher serum glucose and insulin concentrations, and decreased insulin sensitivity as indicated by an increase in HOMA and decrease in QUICKI and Bennett indices. Leptin was significantly increased, but there was no difference in adiponectin (or body condition score). Several significant correlations were found between insulin sensitivity indices, leptin, and serum metabolites identified as significantly different between remission and control cats. No metabolites were significantly correlated with adiponectin. No predictors of relapse were identified in this study. Conclusion and clinical importance: Insulin resistance, an underlying factor in diabetic cats, persists in diabetic remission. Cats in remission should be managed to avoid further exacerbating insulin resistance.
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    Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia (vol 13, 2614, 2022)
    Bassal, MA ; Samaraweera, SE ; Lim, K ; Benard, BA ; Bailey, S ; Kaur, S ; Leo, P ; Toubia, J ; Thompson-Peach, C ; Nguyen, T ; Maung, KZY ; Casolari, DA ; Iarossi, DG ; Pagani, IS ; Powell, J ; Pitson, S ; Natera, S ; Roessner, U ; Lewis, ID ; Brown, AL ; Tenen, DG ; Robinson, N ; Ross, DM ; Majeti, R ; Gonda, TJ ; Thomas, D ; D'Andrea, RJ (NATURE PORTFOLIO, 2022-07-15)
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    The Effect of Cold Stress on the Root-Specific Lipidome of Two Wheat Varieties with Contrasting Cold Tolerance
    Cheong, BE ; Yu, D ; Martinez-Seidel, F ; Ho, WWH ; Rupasinghe, TWT ; Dolferus, R ; Roessner, U (MDPI, 2022-05-01)
    Complex glycerolipidome analysis of wheat upon low temperature stress has been reported for above-ground tissues only. There are no reports on the effects of cold stress on the root lipidome nor on tissue-specific responses of cold stress wheat roots. This study aims to investigate the changes of lipid profiles in the different developmental zones of the seedling roots of two wheat varieties with contrasting cold tolerance exposed to chilling and freezing temperatures. We analyzed 273 lipid species derived from 21 lipid classes using a targeted profiling approach based on MS/MS data acquired from schedule parallel reaction monitoring assays. For both the tolerant Young and sensitive Wyalkatchem species, cold stress increased the phosphatidylcholine and phosphatidylethanolamine compositions, but decreased the monohexosyl ceramide compositions in the root zones. We show that the difference between the two varieties with contrasting cold tolerance could be attributed to the change in the individual lipid species, rather than the fluctuation of the whole lipid classes. The outcomes gained from this study may advance our understanding of the mechanisms of wheat adaptation to cold and contribute to wheat breeding for the improvement of cold-tolerance.
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    Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia.
    Bassal, MA ; Samaraweera, SE ; Lim, K ; Benard, BA ; Bailey, S ; Kaur, S ; Leo, P ; Toubia, J ; Thompson-Peach, C ; Nguyen, T ; Maung, KZY ; Casolari, DA ; Iarossi, DG ; Pagani, IS ; Powell, J ; Pitson, S ; Natera, S ; Roessner, U ; Lewis, ID ; Brown, AL ; Tenen, DG ; Robinson, N ; Ross, DM ; Majeti, R ; Gonda, TJ ; Thomas, D ; D'Andrea, RJ (Springer Science and Business Media LLC, 2022-05-12)
    The interaction of germline variation and somatic cancer driver mutations is under-investigated. Here we describe the genomic mitochondrial landscape in adult acute myeloid leukaemia (AML) and show that rare variants affecting the nuclear- and mitochondrially-encoded complex I genes show near-mutual exclusivity with somatic driver mutations affecting isocitrate dehydrogenase 1 (IDH1), but not IDH2 suggesting a unique epistatic relationship. Whereas AML cells with rare complex I variants or mutations in IDH1 or IDH2 all display attenuated mitochondrial respiration, heightened sensitivity to complex I inhibitors including the clinical-grade inhibitor, IACS-010759, is observed only for IDH1-mutant AML. Furthermore, IDH1 mutant blasts that are resistant to the IDH1-mutant inhibitor, ivosidenib, retain sensitivity to complex I inhibition. We propose that the IDH1 mutation limits the flexibility for citrate utilization in the presence of impaired complex I activity to a degree that is not apparent in IDH2 mutant cells, exposing a mutation-specific metabolic vulnerability. This reduced metabolic plasticity explains the epistatic relationship between the germline complex I variants and oncogenic IDH1 mutation underscoring the utility of genomic data in revealing metabolic vulnerabilities with implications for therapy.
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    Salt stress alters membrane lipid content and lipid biosynthesis pathways in the plasma membrane and tonoplast
    Guo, Q ; Liu, L ; Rupasinghe, TWT ; Roessner, U ; Barkla, BJ (OXFORD UNIV PRESS INC, 2022-03-15)
    Plant cell membranes are the sites of sensing and initiation of rapid responses to changing environmental factors including salinity stress. Understanding the mechanisms involved in membrane remodeling is important for studying salt tolerance in plants. This task remains challenging in complex tissue due to suboptimal subcellular membrane isolation techniques. Here, we capitalized on the use of a surface charge-based separation method, free flow electrophoresis, to isolate the tonoplast (TP) and plasma membrane (PM) from leaf tissue of the halophyte ice plant (Mesembryanthemum crystallinum L.). Results demonstrated a membrane-specific lipidomic remodeling in this plant under salt conditions, including an increased proportion of bilayer forming lipid phosphatidylcholine in the TP and an increase in nonbilayer forming and negatively charged lipids (phosphatidylethanolamine and phosphatidylserine) in the PM. Quantitative proteomics showed salt-induced changes in proteins involved in fatty acid synthesis and desaturation, glycerolipid, and sterol synthesis, as well as proteins involved in lipid signaling, binding, and trafficking. These results reveal an essential plant mechanism for membrane homeostasis wherein lipidome remodeling in response to salt stress contributes to maintaining the physiological function of individual subcellular compartments.
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    Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies.
    Martelli, F ; Hernandes, NH ; Zuo, Z ; Wang, J ; Wong, C-O ; Karagas, NE ; Roessner, U ; Rupasinghe, T ; Robin, C ; Venkatachalam, K ; Perry, T ; Batterham, P ; Bellen, HJ (eLife Sciences Publications, Ltd, 2022-02-22)
    Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synthetic insecticides and is considered less harmful to beneficial insects, yet its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad antagonize its neuronal target, the nicotinic acetylcholine receptor subunit alpha 6 (nAChRα6), reducing the cholinergic response. We show that the nAChRα6 receptors are transported to lysosomes that become enlarged and increase in number upon low doses of spinosad treatment. Lysosomal dysfunction is associated with mitochondrial stress and elevated levels of reactive oxygen species (ROS) in the central nervous system where nAChRα6 is broadly expressed. ROS disturb lipid storage in metabolic tissues in an nAChRα6-dependent manner. Spinosad toxicity is ameliorated with the antioxidant N-acetylcysteine amide. Chronic exposure of adult virgin females to low doses of spinosad leads to mitochondrial defects, severe neurodegeneration, and blindness. These deleterious effects of low-dose exposures warrant rigorous investigation of its impacts on beneficial insects.
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    Modulators or facilitators? Roles of lipids in plant root-microbe interactions
    Macabuhay, A ; Arsova, B ; Walker, R ; Johnson, A ; Watt, M ; Roessner, U (ELSEVIER SCIENCE LONDON, 2022-02-01)
    Lipids have diverse functions in regulating the plasma membrane's cellular processes and signaling mediation. Plasma membrane lipids are also involved in the plant's complex interactions with the surrounding microorganisms, with which plants are in various forms of symbiosis. The roles of lipids influence the whole microbial colonization process, thus shaping the rhizomicrobiome. As chemical signals, lipids facilitate the stages of rhizospheric interactions - from plant root to microbe, microbe to microbe, and microbe to plant root - and modulate the plant's defense responses upon perception or contact with either beneficial or phytopathogenic microorganisms. Although studies have come a long way, further investigation is needed to discover more lipid species and elucidate novel lipid functions and profiles under various stages of plant root-microbe interactions.
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    Metabolomics as an emerging tool to study plant- microbe interactions
    Gupta, S ; Schillaci, M ; Roessner, U (PORTLAND PRESS LTD, 2022-02-22)
    In natural environments, interaction between plant roots and microorganisms are common. These interactions between microbial species and plants inhabited by them are being studied using various techniques. Metabolomics research based on mass spectrometric techniques is one of the crucial approaches that underpins system biology and relies on precision instrument analysis. In the last decade, this emerging field has received extensive attention. It provides a qualitative and quantitative approach for determining the mechanisms of symbiosis of bacteria and fungi with plants and also helps to elucidate the tolerance mechanisms of host plants against various abiotic stresses. However, this -omics application and its tools in plant-microbe interaction studies is still underutilized compared with genomic and transcriptomic methods. Therefore, it is crucial to bring this field forward to bear on the study of plant resistance and susceptibility. This review describes the current status of methods and progress in metabolomics applications for plant-microbe interaction studies discussing current challenges and future prospects.