Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Patient and nurse outcomes and the cost of nurses' turnover in Australian hospitals. An adequate supply of nurses is fundamental to all of the National Health Priority disease areas where quality care cannot be delivered without an adequate number of motivated nurses. Designing cost-effective methods of retaining nurses requires understanding reasons why they leave the workforce and the impact this has on patient care and system costs. The findings will assist policy makers and workforce planner ....Patient and nurse outcomes and the cost of nurses' turnover in Australian hospitals. An adequate supply of nurses is fundamental to all of the National Health Priority disease areas where quality care cannot be delivered without an adequate number of motivated nurses. Designing cost-effective methods of retaining nurses requires understanding reasons why they leave the workforce and the impact this has on patient care and system costs. The findings will assist policy makers and workforce planners at both local and national levels, to design strategies to effectively recruit and retain nurses as demands for health care and market competition for staff both increase.Read moreRead less
The Role Of Corticothalamic Feedback On The Response Dynamics Of Thalamic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
A fundamental question in neuroscience is how the brain selectively processes sensory information to generate a reliable representation of the world. Positioned in the centre of the brain, the thalamus plays a key role in sensory processing. This project investigates how the interaction between thalamus and cortex shapes the selection and gating of sensory information. This is a fundamental question in basic neuroscience with the potential to increase our knowledge about attentional deficits.
Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Discovery Early Career Researcher Award - Grant ID: DE230100085
Funder
Australian Research Council
Funding Amount
$440,954.00
Summary
Forensic genomic toolkit for tracking the illegal wildlife trade. This project aims to analyse the illegal parrot trade by utilising conservation genomic approaches. The project will reveal wildlife trade routes in South-east Asia by developing cutting-edge forensic genomic techniques and criminological methods. Expected outcomes of this project include new field-deployable sequencing technology to provide in-situ genetic information for identifying the taxonomy and provenance of confiscated spe ....Forensic genomic toolkit for tracking the illegal wildlife trade. This project aims to analyse the illegal parrot trade by utilising conservation genomic approaches. The project will reveal wildlife trade routes in South-east Asia by developing cutting-edge forensic genomic techniques and criminological methods. Expected outcomes of this project include new field-deployable sequencing technology to provide in-situ genetic information for identifying the taxonomy and provenance of confiscated specimens, and a first ever genetic database of traded wildlife. The project will facilitate important countermeasures to the illegal wildlife trade including confiscation, reintroduction, improved law enforcement, and education for better biodiversity outcomes in our region.Read moreRead less
The Molecular Basis of Nanoparticle Resistance in Mixed-Species Biofilm. The project aims to understand how the globally significant mixed-species growth of pathogens develop resistance to silver nanoparticle, currently one of the most important alternative antimicrobials to antibiotics. The integrated research is to elucidate, for the first time, the nanoparticle multi-targeting toxicity on mixed-species bacterial community and how, in turn, the bacteria activate their cell-to-cell signalling f ....The Molecular Basis of Nanoparticle Resistance in Mixed-Species Biofilm. The project aims to understand how the globally significant mixed-species growth of pathogens develop resistance to silver nanoparticle, currently one of the most important alternative antimicrobials to antibiotics. The integrated research is to elucidate, for the first time, the nanoparticle multi-targeting toxicity on mixed-species bacterial community and how, in turn, the bacteria activate their cell-to-cell signalling for a synergistic defence to adapt to the nanoparticle toxicity. The pioneering knowledge is the foundation for technologies targeting the interspecies metabolite cross-talking to overcome the resistance phenomena, ensuring a long-term efficacy of the alternative antimicrobial on the difficult-to-control pathogenic growth.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100015
Funder
Australian Research Council
Funding Amount
$430,000.00
Summary
Australian Facility for Taphonomic Experimental Research . Australian facility for taphonomic experimental research: The aim of this project is to establish a unique Australian research facility dedicated to studying the physical, chemical, and biological processes of human decomposition. This facility will be the first of its kind in Australia and the Southern Hemisphere, drawing together a collaborative team of experts in a broad range of taphonomy disciplines. The results of the research are ....Australian Facility for Taphonomic Experimental Research . Australian facility for taphonomic experimental research: The aim of this project is to establish a unique Australian research facility dedicated to studying the physical, chemical, and biological processes of human decomposition. This facility will be the first of its kind in Australia and the Southern Hemisphere, drawing together a collaborative team of experts in a broad range of taphonomy disciplines. The results of the research are expected to advance our limited understanding of the taphonomic processes acting on remains in a natural Australian environment. The outcomes will assist police and forensic services to improve their procedures for searching, locating, recovering, and identifying missing persons, victims of homicide, and victims of disaster on both a national and international scale.Read moreRead less