School of BioSciences - Research Publications

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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.
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    Characterization of epidermal bladder cells in Chenopodium quinoa
    Otterbach, SL ; Khoury, H ; Rupasinghe, T ; Mendis, H ; Kwan, KH ; Lui, V ; Natera, SHA ; Klaiber, I ; Allen, NM ; Jarvis, DE ; Tester, M ; Roessner, U ; Schmoeckel, SM (WILEY, 2021-10-05)
    Chenopodium quinoa (quinoa) is considered a superfood with its favourable nutrient composition and being gluten free. Quinoa has high tolerance to abiotic stresses, such as salinity, water deficit (drought) and cold. The tolerance mechanisms are yet to be elucidated. Quinoa has epidermal bladder cells (EBCs) that densely cover the shoot surface, particularly the younger parts of the plant. Here, we report on the EBC's primary and secondary metabolomes, as well as the lipidome in control conditions and in response to abiotic stresses. EBCs were isolated from plants after cold, heat, high-light, water deficit and salt treatments. We used untargeted gas chromatography-mass spectrometry (GC-MS) to analyse metabolites and untargeted and targeted liquid chromatography-MS (LC-MS) for lipids and secondary metabolite analyses. We identified 64 primary metabolites, including sugars, organic acids and amino acids, 19 secondary metabolites, including phenolic compounds, betanin and saponins and 240 lipids categorized in five groups including glycerolipids and phospholipids. We found only few changes in the metabolic composition of EBCs in response to abiotic stresses; these were metabolites related with heat, cold and high-light treatments but not salt stress. Na+ concentrations were low in EBCs with all treatments and approximately two orders of magnitude lower than K+ concentrations.
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    Reproductive Stage Drought Tolerance in Wheat: Importance of Stomatal Conductance and Plant Growth Regulators
    Onyemaobi, O ; Sangma, H ; Garg, G ; Wallace, X ; Kleven, S ; Suwanchaikasem, P ; Roessner, U ; Dolferus, R (MDPI, 2021-11-01)
    Drought stress requires plants to adjust their water balance to maintain tissue water levels. Isohydric plants ('water-savers') typically achieve this through stomatal closure, while anisohydric plants ('water-wasters') use osmotic adjustment and maintain stomatal conductance. Isohydry or anisohydry allows plant species to adapt to different environments. In this paper we show that both mechanisms occur in bread wheat (Triticum aestivum L.). Wheat lines with reproductive drought-tolerance delay stomatal closure and are temporarily anisohydric, before closing stomata and become isohydric at higher threshold levels of drought stress. Drought-sensitive wheat is isohydric from the start of the drought treatment. The capacity of the drought-tolerant line to maintain stomatal conductance correlates with repression of ABA synthesis in spikes and flag leaves. Gene expression profiling revealed major differences in the drought response in spikes and flag leaves of both wheat lines. While the isohydric drought-sensitive line enters a passive growth mode (arrest of photosynthesis, protein translation), the tolerant line mounts a stronger stress defence response (ROS protection, LEA proteins, cuticle synthesis). The drought response of the tolerant line is characterised by a strong response in the spike, displaying enrichment of genes involved in auxin, cytokinin and ethylene metabolism/signalling. While isohydry may offer advantages for longer term drought stress, anisohydry may be more beneficial when drought stress occurs during the critical stages of wheat spike development, ultimately improving grain yield.
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    Epidermal bladder cells confer salinity stress tolerance in the halophyte quinoa and Atriplex species
    Kiani-Pouya, A ; Roessner, U ; Jayasinghe, NS ; Lutz, A ; Rupasinghe, T ; Bazihizina, N ; Bohm, J ; Alharbi, S ; Hedrich, R ; Shabala, S (WILEY, 2017-09-01)
    Epidermal bladder cells (EBCs) have been postulated to assist halophytes in coping with saline environments. However, little direct supporting evidence is available. Here, Chenopodium quinoa plants were grown under saline conditions for 5 weeks. One day prior to salinity treatment, EBCs from all leaves and petioles were gently removed by using a soft cosmetic brush and physiological, ionic and metabolic changes in brushed and non-brushed leaves were compared. Gentle removal of EBC neither initiated wound metabolism nor affected the physiology and biochemistry of control-grown plants but did have a pronounced effect on salt-grown plants, resulting in a salt-sensitive phenotype. Of 91 detected metabolites, more than half were significantly affected by salinity. Removal of EBC dramatically modified these metabolic changes, with the biggest differences reported for gamma-aminobutyric acid (GABA), proline, sucrose and inositol, affecting ion transport across cellular membranes (as shown in electrophysiological experiments). This work provides the first direct evidence for a role of EBC in salt tolerance in halophytes and attributes this to (1) a key role of EBC as a salt dump for external sequestration of sodium; (2) improved K+ retention in leaf mesophyll and (3) EBC as a storage space for several metabolites known to modulate plant ionic relations.