ORCID Profile
0000-0001-7360-6466
Current Organisation
Peter Doherty Institute
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.
Publisher: Wiley
Date: 25-12-2018
DOI: 10.1002/DTA.2554
Abstract: CJC-1295 is a 30 amino acid peptide-based drug that stimulates the release of growth hormone (GH) from the pituitary gland. It is unique among performance-enhancing peptides due to the presence of a reactive maleimidopropionic acid group that covalently links the peptide to free thiols on the surface of plasma proteins. Once conjugated, CJC-1295 remains active in the bloodstream for significantly longer than non-conjugated peptide-based drugs that are rapidly excreted. Conjugation of CJC-1295 to plasma proteins prevents its detection by top-down mass-spectrometry-based peptide screening protocols as it effectively becomes a macromolecular protein with an undefined molecular weight. Using a pair of monoclonal antibodies raised against the CJC-1295 peptide, we present an immuno-polymerase chain reaction (I-PCR) assay that is capable of detecting the CJC-1295-protein conjugate at concentrations down to 0.8 pg/mL. Detection of endogenous equine GHRH necessitated a screening threshold for CJC-1295 in equine plasma of 50 pg/mL. The effectiveness of the assay for controlling the illicit use of CJC-1295 was confirmed in equine blood s les after administration in thoroughbred race horses.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5AN02544C
Abstract: A comparison of complementary methods to quantify biometals per in idual for analytical biochemical studies using microscopic model organisms.
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1039/C6MT00189K
Abstract: Otoliths, the biomineralised hearing "ear stones" from the inner ear of fish, grow throughout the lifespan of an in idual, with deposition of alternating calciferous and proteinaceous bands occurring daily. Trace element : calcium ratios within daily increments measured by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) are often used in fisheries science to reconstruct environmental histories. There is, however, considerable uncertainty as to which elements are interacting with either the proteinaceous or calciferous zones of the otolith, and thus their utility as indicators of environmental change. To answer this, we used size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) of endolymph, the otolith growth medium, to determine the binding interactions for a range of elements. In addition, we used solution ICP-MS to quantify element concentrations in paired otolith and endolymph s les and determined relative enrichment factors for each. We found 12 elements that are present only in the proteinaceous fraction, 6 that are present only in the salt fraction, and 4 that are present in both. These findings have important implications for the reconstruction of environmental histories based on changes in otolith elemental composition: (1) elements occurring only in the salt fraction are most likely to reflect changes in the physico-chemical environment experienced during life (2) elements occurring only in the proteinaceous fraction are more likely to reflect physiological rather than environmental events and (3) elements occurring in both the salt and proteinaceous fractions are likely to be informative about both endogenous and exogenous processes, potentially reducing their utility in environmental reconstructions.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2022
DOI: 10.1038/S41418-022-01003-1
Abstract: Mutations in presenilin 1 and 2 ( PS1 and PS2 ) cause autosomal dominant familial Alzheimer’s disease (FAD). Ferroptosis has been implicated as a mechanism of neurodegeneration in AD since neocortical iron burden predicts Alzheimer’s disease (AD) progression. We found that loss of the presenilins dramatically sensitizes multiple cell types to ferroptosis, but not apoptosis. FAD causal mutations of presenilins similarly sensitizes cells to ferroptosis. The presenilins promote the expression of GPX4, the selenoprotein checkpoint enzyme that blocks ferroptosis by quenching the membrane propagation of lethal hydroperoxyl radicals. Presenilin γ-secretase activity cleaves Notch-1 to signal LRP8 expression, which then controls GPX4 expression by regulating the supply of selenium into the cell since LRP8 is the uptake receptor for selenoprotein P. Selenium uptake is thus disrupted by presenilin FAD mutations, suppressing GPX4 expression. Therefore, presenilin mutations may promote neurodegeneration by derepressing ferroptosis, which has implications for disease-modifying therapeutics.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-08-2021
Abstract: Bacterial manganese import is achieved by unique architectural features that are conserved across the kingdoms of life.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2017
DOI: 10.1038/MP.2017.171
Abstract: Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
Publisher: Oxford University Press (OUP)
Date: 2019
DOI: 10.1039/C9MT00201D
Abstract: Electrospray ionisation mass spectrometry (ESI-MS) is an alternative to inductively coupled plasma mass spectrometry (ICP-MS) to better understand selenium biochemistry.
Publisher: American Society for Microbiology
Date: 23-02-2021
Abstract: Zinc is an essential nutrient for the virulence of bacterial pathogens such as Streptococcus pneumoniae . Many Gram-positive bacteria use a two-domain lipoprotein for zinc acquisition, but how this class of metal-recruiting proteins acquire zinc and interact with the uptake machinery has remained poorly defined.
Location: Australia
No related grants have been discovered for Katherine Ganio.