ORCID Profile
0000-0003-1235-0879
Current Organisation
Harry Perkins Institute of Medical Research Perkins South
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Measurements of WH and ZH production in the $$H \rightarrow b\bar{b}$$ decay channel in pp collisions at $$13\,\text {Te}\text {V}$$ with the ATLAS detector
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1140/EPJC/S10052-020-08677-2
Abstract: Measurements of the Standard Model Higgs boson decaying into a $$b\\bar{b}$$ b b ¯ pair and produced in association with a W or Z boson decaying into leptons, using proton–proton collision data collected between 2015 and 2018 by the ATLAS detector, are presented. The measurements use collisions produced by the Large Hadron Collider at a centre-of-mass energy of $$\\sqrt{s} = 13\\,\\text {Te}\\text {V}$$ s = 13 Te , corresponding to an integrated luminosity of $$139\\,\\mathrm {fb}^{-1}$$ 139 fb - 1 . The production of a Higgs boson in association with a W or Z boson is established with observed (expected) significances of 4.0 (4.1) and 5.3 (5.1) standard deviations, respectively. Cross-sections of associated production of a Higgs boson decaying into bottom quark pairs with an electroweak gauge boson, W or Z , decaying into leptons are measured as a function of the gauge boson transverse momentum in kinematic fiducial volumes. The cross-section measurements are all consistent with the Standard Model expectations, and the total uncertainties vary from 30% in the high gauge boson transverse momentum regions to 85% in the low regions. Limits are subsequently set on the parameters of an effective Lagrangian sensitive to modifications of the WH and ZH processes as well as the Higgs boson decay into $$b\\bar{b}$$ b b ¯ .
Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation
Publisher: EMBO
Date: 13-11-2019
Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals
Publisher: eLife Sciences Publications, Ltd
Date: 14-11-2017
DOI: 10.7554/ELIFE.30952
Abstract: Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment.
CirGO: An alternative circular way of visualising gene ontology terms
Publisher: Springer Science and Business Media LLC
Date: 18-02-2019
Measurements of sensor radiation damage in the ATLAS inner detector using leakage currents
Publisher: IOP Publishing
Date: 08-2021
DOI: 10.1088/1748-0221/16/08/P08025
Abstract: Non-ionizing energy loss causes bulk damage to the silicon sensors of the ATLAS pixel and strip detectors. This damage has important implications for data-taking operations, charged-particle track reconstruction, detector simulations, and physics analysis. This paper presents simulations and measurements of the leakage current in the ATLAS pixel detector and semiconductor tracker as a function of location in the detector and time, using data collected in Run 1 (2010–2012) and Run 2 (2015–2018) of the Large Hadron Collider. The extracted fluence shows a much stronger | z |-dependence in the innermost layers than is seen in simulation. Furthermore, the overall fluence on the second innermost layer is significantly higher than in simulation, with better agreement in layers at higher radii. These measurements are important for validating the simulation models and can be used in part to justify safety factors for future detector designs and interventions.
Measurements of W+W−+ ≥ 1 jet production cross-sections in pp collisions at $$ \sqrt{s} $$ = 13 TeV with the ATLAS detector
Publisher: Springer Science and Business Media LLC
Date: 06-2021
Abstract: Fiducial and differential cross-section measurements of W + W − production in association with at least one hadronic jet are presented. These measurements are sensitive to the properties of electroweak-boson self-interactions and provide a test of perturbative quantum chromodynamics and the electroweak theory. The analysis is performed using proton-proton collision data collected at $$ \sqrt{s} $$ s = 13 TeV with the ATLAS experiment, corresponding to an integrated luminosity of 139 fb − 1 . Events are selected with exactly one oppositely charged electron-muon pair and at least one hadronic jet with a transverse momentum of p T 30 GeV and a pseudorapidity of | η | 4 . 5. After subtracting the background contributions and correcting for detector effects, the jet-inclusive W + W − + ≥ 1 jet fiducial cross-section and W + W − + jets differential cross-sections with respect to several kinematic variables are measured. These measurements include leptonic quantities, such as the lepton transverse momenta and the transverse mass of the W + W − system, as well as jet-related observables such as the leading jet transverse momentum and the jet multiplicity. Limits on anomalous triple-gauge-boson couplings are obtained in a phase space where interference between the Standard Model litude and the anomalous litude is enhanced.
Simultaneous processing and degradation of mitochondrial RNAs revealed by circularized RNA sequencing
Publisher: Oxford University Press (OUP)
Date: 15-02-2017
DOI: 10.1093/NAR/GKX104
Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.CELREP.2016.07.031
Abstract: The regulation of mitochondrial RNA processing and its importance for ribosome biogenesis and energy metabolism are not clear. We generated conditional knockout mice of the endoribonuclease component of the RNase P complex, MRPP3, and report that it is essential for life and that heart and skeletal-muscle-specific knockout leads to severe cardiomyopathy, indicating that its activity is non-redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing, and this is required for the correct biogenesis of the mitochondrial ribosomal subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA containing the 16S rRNA. Taken together, our data show that RNA processing links transcription to translation via assembly of the mitoribosome.
Investigating Mitochondrial Transcriptomes and RNA Processing Using Circular RNA Sequencing
Publisher: Springer US
Date: 24-11-2021
PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.CELREP.2018.03.033
Abstract: The regulation of mitochondrial RNA life cycles and their roles in ribosome biogenesis and energy metabolism are not fully understood. We used CRISPR/Cas9 to generate heart- and skeletal-muscle-specific knockout mice of the pentatricopeptide repeat domain protein 1, PTCD1, and show that its loss leads to severe cardiomyopathy and premature death. Our detailed transcriptome-wide and functional analyses of these mice enabled us to identify the molecular role of PTCD1 as a 16S rRNA-binding protein essential for its stability, pseudouridylation, and correct biogenesis of the mitochondrial large ribosomal subunit. We show that impaired mitoribosome biogenesis can have retrograde signaling effects on nuclear gene expression through the transcriptional activation of the mTOR pathway and upregulation of cytoplasmic protein synthesis and pro-survival factors in the absence of mitochondrial translation. Taken together, our data show that impaired assembly of the mitoribosome exerts its consequences via differential regulation of mitochondrial and cytoplasmic protein synthesis.
Measurements of differential cross-sections in four-lepton events in 13 TeV proton-proton collisions with the ATLAS detector
Publisher: Springer Science and Business Media LLC
Date: 07-2021
Abstract: Measurements of four-lepton differential and integrated fiducial cross-sections in events with two same-flavour, opposite-charge electron or muon pairs are presented. The data correspond to 139 fb − 1 of $$ \\sqrt{s} $$ s = 13 TeV proton-proton collisions, collected by the ATLAS detector during Run 2 of the Large Hadron Collider (2015–2018). The final state has contributions from a number of interesting Standard Model processes that dominate in different four-lepton invariant mass regions, including single Z boson production, Higgs boson production and on-shell ZZ production, with a complex mix of interference terms, and possible contributions from physics beyond the Standard Model. The differential cross-sections include the four-lepton invariant mass inclusively, in slices of other kinematic variables, and in different lepton flavour categories. Also measured are dilepton invariant masses, transverse momenta, and angular correlation variables, in four regions of four-lepton invariant mass, each dominated by different processes. The measurements are corrected for detector effects and are compared with state-of-the-art Standard Model calculations, which are found to be consistent with the data. The Z → 4 ℓ branching fraction is extracted, giving a value of (4 . 41 ± 0 . 30) × 10 − 6 . Constraints on effective field theory parameters and a model based on a spontaneously broken B − L gauge symmetry are also evaluated. Further reinterpretations can be performed with the provided information.
Measurements of top-quark pair single- and double-differential cross-sections in the all-hadronic channel in pp collisions at $$ \sqrt{\mathrm{s}} $$ = 13 TeV using the ATLAS detector
Publisher: Springer Science and Business Media LLC
Date: 2021
Abstract: Differential cross-sections are measured for top-quark pair production in the all-hadronic decay mode, using proton-proton collision events collected by the ATLAS experiment in which all six decay jets are separately resolved. Absolute and normalised single- and double-differential cross-sections are measured at particle and parton level as a function of various kinematic variables. Emphasis is placed on well-measured observables in fully reconstructed final states, as well as on the study of correlations between the top-quark pair system and additional jet radiation identified in the event. The study is performed using data from proton-proton collisions at $$ \\sqrt{s} $$ s = 13 TeV collected by the ATLAS detector at CERN’s Large Hadron Collider in 2015 and 2016, corresponding to an integrated luminosity of 36.1 fb − 1 . The rapidities of the in idual top quarks and of the top-quark pair are well modelled by several independent event generators. Significant mismodelling is observed in the transverse momenta of the leading three jet emissions, while the leading top-quark transverse momentum and top-quark pair transverse momentum are both found to be incompatible with several theoretical predictions.
Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan
Publisher: Wiley
Date: 07-06-2021
DOI: 10.1111/ACEL.13408
Abstract: Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high‐fat diet modulates mitochondrial translation and affects lifespan in mutant mice with error‐prone ( Mrps12 ep / ep ) or hyper‐accurate ( Mrps12 ha / ha ) mitochondrial ribosomes. Intriguingly, although both mutations are metabolically beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance during a high‐fat diet, they manifest ergent (either deleterious or beneficial) outcomes in a tissue‐specific manner. In two distinct organs that are commonly affected by the metabolic disease, the heart and the liver, Mrps12 ep / ep mice were protected against heart defects but sensitive towards lipid accumulation in the liver, activating genes involved in steroid and amino acid metabolism. In contrast, enhanced translational accuracy in Mrps12 ha / ha mice protected the liver from a high‐fat diet through activation of liver proliferation programs, but enhanced the development of severe hypertrophic cardiomyopathy and led to reduced lifespan. These findings reflect the complex transcriptional and cell signalling responses that differ between post‐mitotic (heart) and highly proliferative (liver) tissues. We show trade‐offs between the rate and fidelity of mitochondrial protein synthesis dictate tissue‐specific outcomes due to commonly encountered stressful environmental conditions or aging.
Fidelity of translation initiation is required for coordinated respiratory complex assembly
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-12-2019
Abstract: The initiation of mitochondrial protein synthesis fine-tunes the assembly of respiratory complexes and energy production.
Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z
Publisher: EMBO
Date: 20-08-2018
Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at $$\sqrt{s}=13\,\text {TeV}$$
Publisher: Springer Science and Business Media LLC
Date: 06-2021
DOI: 10.1140/EPJC/S10052-021-09192-8
Abstract: The paper presents a measurement of the Standard Model Higgs Boson decaying to b -quark pairs in the vector boson fusion (VBF) production mode. A s le corresponding to 126 $$\\hbox {fb}^{-1}$$ fb - 1 of $$\\sqrt{s} = 13\\,\\text {TeV}$$ s = 13 TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be $$0.95^{+0.38}_{-0.36}$$ 0 . 95 - 0.36 + 0.38 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b -quarks, produced via VBF in association with a photon.
Related Organisations
The University Of Western Australia Medical School
Location: Australia
Harry Perkins Institute Of Medical Research Perkins South
Location: Australia
Saint Petersburg State University Of Cinema And Television
Location: Russian Federation
Related Funding Activities
No related grants have been discovered for Irina Kuznetsova.