In 2012, Mixed lineage kinase domain-like (MLKL), a catalytically-dead (“zombie”) cousin of conventional protein kinases, termed a pseudokinase, was implicated as the key effector in the programmed necrosis (or necroptosis) cell death pathway. This pathway has been implicated in innate immunity, the pathogenesis of inflammatory diseases, and tissue injury arising from ischemia-reperfusion. As...
Milk is our sole source of nutrition for the first six months of life and milk lipids carry fat-soluble nutrients through the gut as well as providing most of the energy we consume with milk. The digestion and absorption of lipids, predominantly triglycerides, and entrained nutrients is therefore important for survival and growth. Milk triglycerides are regarded amongst the most chemically...
Hepatocytes are essential for maintaining homeostasis of mammalian iron and lipid metabolism. Serious health consequences have been linked to dysregulation of both areas. One such consequence is non-alcoholic fatty liver disease (NAFLD). Approximately 30% of individuals with NAFLD demonstrate a moderate increase in hepatic iron; however, the mechanism and metabolic consequences remain...
Research into treatment for Duchenne Muscular Dystrophy (DMD) typically focuses on deterioration of muscle, however bone health is also severely compromised. Current treatment with corticosteroids exacerbate bone loss, so novel therapies targeting both muscle and bone are needed. Studies on bone health in a pre-clinical model, mdx mice, are limited and have conflicting results.
Objective of...
Iron is an essential trace element that, when in excess, becomes highly toxic [1]. Intracellular iron concentration must be strictly regulated by a network of interacting mechanisms [2]. Ferritin is a ubiquitous iron-storage protein that forms a highly conserved 24-subunit spherical cage-like structure. Ferritin catalyses the oxidation of iron (II) to iron (III) and sequesters the newly...
Alzheimer’s disease is the most common form of dementia and poses significant health and economic concerns. Currently, the disease has no cure, and it is expected that over 1 million people could be affected by 2058 in Australia alone. The content and distribution of metals such as Fe, Cu, Zn is known to change in the ageing brain and thus, increased understanding of the mechanistic role of...
Breast microcalcifications are an important primary radiological indicator of breast cancer. However, microcalcification classification and diagnosis can be still challenging for radiologists due to limitations of the standard 2D mammography technique, including spatial and contrast resolution. In this study, we propose an approach to improve the detection of microcalcifications in...
Pollen-induced thunderstorm asthma outbreaks affect thousands of individuals globally. Australians in particular suffer from it every year. Pollens, the major culprit in thunderstorm asthma, are biological microparticles produced by flowering species of the plants. Pollens encounter stormy environments including lightning and humidity in thunderstorms, which results in liberation of associated...
Zinc plays an important function in glucose regulation, particularly within pancreatic islets, the anatomical home of the glucose regulating hormones insulin and glucagon. Glucose dysregulation is a significant contributor to the epidemic of metabolic diseases, including diabetes, that affect an increasing number of people. Zn is found in very high (mM) concentrations in insulin-secreting...
High-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA...
Bacteria use folding enzymes to produce functional virulence factors. These foldases include the Dsb family of proteins, which catalyze a key step in the protein-folding pathway, the introduction of disulfide bonds. The Dsb oxidative system, which includes an oxidative DsbA/DsbB pathway and an isomerase DsbC/DsbD pathway, is present in numerous bacterial species. Conventionally, Dsb proteins...
Necroptosis is a lytic programmed cell death pathway with origins in innate immunity that is frequently dysregulated in inflammatory diseases. The terminal effector of the pathway, MLKL, is licensed to kill following phosphorylation of its pseudokinase domain by the upstream regulator, RIPK3 kinase. Phosphorylation provokes the unleashing of MLKL’s N-terminal four-helix bundle (4HB or HeLo)...
The immune system is vigilant in detecting foreign pathogens. Our cells present peptides (p), small fragments of proteins, atop Major Histocompatibility Complex (MHC) glycoproteins. These pMHC molecules are displayed on the cell’s surface and monitored by T cells of the immune system that patrol the body. T cells use their specialized T cell receptors (TCRs) to recognize and bind to pMHCs,...
Propagation-based phase-contrast computed tomography (PB-CT) has the potential to improve breast cancer detection and characterisation compared to established mammography techniques. The aim of this work is to find a quantitative image quality metric which could accurately predict the subjective clinical image quality assessment of PB-CT images made by radiologists as described in Taba et al....
Necroptosis is a caspase-independent form of programmed cell death that results in the compromise of plasma membranes and release of inflammatory cellular contents. Dysregulated necroptosis has been shown to play a role in a range of different human pathologies, including ischemia-reperfusion injury, inflammatory diseases, and inflammatory bowel disease. Phosphorylation of MLKL by the RIPK3...
Introduction
Treatment of deadly cancers that are deep-seated within sensitive healthy tissue is limited to adequate targeting strategies. More specifically, brain and central nervous system cancers can be the most aggressive, have higher mortality rates and lower accessibility to chemotherapeutic drugs. This study introduces the first in-depth analysis doped lanthanum manganite (LAGMO)...
COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30 % of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by...
Maturational changes in feeding behaviour among sharks are associated with increased mineralisation of the teeth and jaws, but this relationship has only been demonstrated in a few species. Large, highly mobile shark species are rarely available for detailed anatomical study, despite their importance for ecological health and widespread interest among the general population. We examined the...
Synchrotron CT dose reduction was investigated for the IMBL wiggler source operated at lower magnetic field strength and for beam modulation with spatial filters placed upstream from the sample. Beam quality at 25-30 keV for 1.4-3.0 T was assessed using transmission measurements with copper to quantify the influence of third harmonic radiation. The low energy operational limit is 24-28 keV for...
Gene vectors to treat cystic fibrosis lung disease should be targeted to the conducting airways, as peripheral lung transduction does not offer therapeutic benefit. Viral transduction efficiency is directly related to the vector residence time. However, delivered fluids such as gene vectors naturally spread to the alveoli during inspiration. Extending gene vector residence time within the...
In the fight against drug resistant pathogenic bacterial and fungal cells, low dimensional materials have been shown as a promising form of alternative treatment method. Specifically, few-layer black phosphorus (BP) has demonstrated its effectiveness against a wide range of pathogenic bacteria and fungal cells. In this work, the complex biochemical interaction of BP with a series of microbial...
Passing the site of a bushfire a couple of weeks after it has burnt itself out, you may notice a mass seed germination event taking place, allowing the bush to completely come back to life. This fascinating phenomenon occurs due to compounds in bushfire smoke called karrikins, which act as triggers for seed germination.
Although we know this process occurs, we don’t understand how karrikins...
Regional Lung volume is a key parameter in assessing lung function and health. Computed Tomography (CT) is considered the gold standard for measuring lung volume; however, it requires a relatively high radiation dose and typically has associated lower spatial and temporal resolution than X-ray projection imaging. In this work, we investigate whether regional lung volumes can be determined...
High resolution imaging mass spectrometry by nanoSIMS (nano scale secondary ion mass spectrometry) is a valuable method to observe deuterium accumulation in any number of sample types. NanoSIMS analysis is a high resolution isotope and elemental imaging technique for solid sample surfaces, allows for spatial resolution as low as 50nm and has high sensitivity which makes it an ideal method for...
Polysaccharides are semi-flexible polymers composed of sugar residues with a myriad of important functions in-vivo, including structural support, energy storage and immunogenicity. The local conformation of such chains is a crucial factor governing their interactions. Traditionally this conformation has only been directly accessible in the solid-state, using crystallographic techniques such as...
Radiation exposure is a major limiting factor for long duration manned space flights.
Radiation protection standards are based on the assumption that individuals are equally resistant to ionizing radiation. However, for over a century, there is evidence that humans do not respond equally to radiation. Particularly, the studies of secondary effects post-radiotherapy have shown a great...
A rapidly aging population, high incidence of osteoporosis and trauma-related fractures, and better health care access explain rapid surge in utilisation of orthopedic implantable devices. Unfortunately, many implants fail without strategies that synergistically prevent infections and enhance the implant’s integration with host tissues. Here, we propose a solution that builds on our pioneering...
Our poor understanding of the mechanism by which the peptide-hormone H2 relaxin activates its G protein-coupled receptor, RXFP1 and the related receptor RXFP2, has hindered progress in its therapeutic development. Both receptors possess unique ectodomains that comprise of an N-terminal LDLa module joined by a linker to a Leucine Rich Repeat (LRR) domain. Truncation of the N-terminal LDLa...
In response to the COVID-19 pandemic the Biospectroscopy group within the Monash School of Chemistry have become part of a research working group headed by Prof. Dale Godfrey and Prof. Damian Purcell at the Doherty Institute to develop a new IR diagnostic for the detection of COVID-19. An infrared-based test would be reagent-less, able to test hundreds of thousands using the same instrument,...
Plants, particularly agricultural crops require a number of different elemental macro and micro-nutrients, such as K, Ca, Fe, Mn, Cu, and Zn, to name a few, for health and sustained crop yields. While these nutrients are essential for plant development and growth, they also facilitate pathogen development and progression. Plant pathogens have evolved numerous mechanisms to source essential...
For the first time, starch biosynthesis in genetically modified yeast has been used to produce deuterated starch by growing the yeast in deuterated media at the National Deuteration Facility (NDF) at ANSTO.
Current deuteration methods target the outer starch granule structure, or destroy the layered granular structure entirely. Our methods of deuteration targeted the entire structure of the...
The SARS-CoV-2 virus is the cause of the ongoing Coronavirus disease 19 (COVID-19) pandemic, which causes pneumonia and lower respiratory tract infections (ARDS). To understand the pathogenicity and mode of action of SARS-CoV-2, it is important to portray the whole repertoire of expressed viral proteins. Recent studies showed that the SARS-CoV-2 leader protein Nsp1 has a role in shutting down...
