The Construction And Validation Of The Assessment Of Mental Health Related Quality Of Life (PsyQoL) Instrument
Funder
National Health and Medical Research Council
Funding Amount
$539,450.00
Summary
Mental Health is one of the national health priority areas as well as one of the largest contributors to burden of disease. WHO projections suggest that by 2020 the burden of depression alone will be second only to cardiovascular disease. New treatments for mental disorders are being developed which must be evaluated. Current research methods do not allow an accurate comparison of the cost effectiveness of these therapies with the cost effectiveness of other medical services as this requires the ....Mental Health is one of the national health priority areas as well as one of the largest contributors to burden of disease. WHO projections suggest that by 2020 the burden of depression alone will be second only to cardiovascular disease. New treatments for mental disorders are being developed which must be evaluated. Current research methods do not allow an accurate comparison of the cost effectiveness of these therapies with the cost effectiveness of other medical services as this requires the measurement of 'utility' or 'quality of life'. The small number of 'generic' 'quality of life instruments' developed to date vary significantly in their 'sensitivity' to different illnesses-their ability to detect change-and none is very sensitive to changes in mental health states. The present project is to overcome this deficit. This will be achieved by refining and expanding an instrument developed in Australia, the Assessment of Quality of Life (AQoL) instrument. This is the only instrument to date which was both constructed using correct psychometric principles of instrument construction and which describes health states in terms of the effect upon a patient's ability to function in a social environment. The new instrument called the PsyQoL will increase instrument sensitivity by including a mental health 'module' to the existing instrument and revising existing items. The methods used will include several methodological innovations in the description of health states and the derivation of utility scores. The project will include a large scale 'validation' study which will include the construction of population 'norms' and also the creation of 'exchange rates' between the PsyQoL and other instrument scores. The significance of the project is that the PsyQoL will allow valid and reliable measurement of health states in a way that creates a 'level playing field' between mental and other health related interventions.Read moreRead less
Copy Number Analysis Of Patients With Gonadal Abnormalities Using High Density Microarrays And MLPA
Funder
National Health and Medical Research Council
Funding Amount
$311,187.00
Summary
Congenital conditions in which development of the gonads or anatomical sex is abnormal are surprisingly common. The underlying cause of these problems is most often the failure of genes responsible for proper development of testes or ovaries. Only a small proportion of patients can be explained by mutations in known gonad determining genes. We will analyse DNA from these patients on very high density microarrays to identify new genes that cause abnormalities in testis and ovary development.
Transport Pathways Of Host-derived Iron In Schistosomes Parasites
Funder
National Health and Medical Research Council
Funding Amount
$322,091.00
Summary
This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular resp ....This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular response induced by parasite eggs trapped in body organs is the major cause of chronic human disease. We have discovered two intriguing phenomena of iron metabolism in schistosomes. Firstly, schistosomes have a greater reliance on iron than many other organisms, storing a surfeit in cells that produce the protein-rich egg shell. Secondly, a major transmembrane iron transporter of the parasites, thought to be involved in the uptake of iron, is found on the parasite external body surface and not in the parasite intestine. The extensive nutritional dependence of these worms on iron and the surface location of mediators of iron uptake raise the exciting possibility that we have uncovered a novel system that might be exploited for vaccine or drug-mediated control of these significant human parasites. If we can dissect the pathways schistosomes use to derive iron from their hosts, we may be able to generate vaccines to block this nutritional pathway, or use drugs to block embryogenesis. This project is a fact-finding mission that asks if the host-interactive tegument of these parasites is a major source of metabolic iron. Molecules we demonstrate to be present on the surface will be tested as vaccine candidates in mouse vaccine trialsRead moreRead less
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Dissecting The Role Of Hedgehog Signalling In Chondrogenesis And Skeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
There are close to 400 inherited disorders that affect how the skeleton develops, as well as a range of injury and age-related skeletal defects. There is much interest in treating such abnormalities with artificial bone grown outside the body. In order to achieve this aim we must understand all of the processes involved in producing and maintaining bone within the body. We are using both mouse and cell culture models of skeletal development to increase our understanding of these processes.
ROLE OF PROTEASE ACTIVATED RECEPTORS IN CYSTIC FIBROSIS LUNG PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$176,521.00
Summary
Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the ....Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the respiratory epithelium. These, in turn, stimulate the movement of neutrophils from the blood to the lung where damage then ensues. How these proteases stimulate release is unclear but studies suggest other proteases involved in inflammation induce release through their interaction with a novel group of protease activated receptors (PAR). In this study, we wish to determine whether PAR are activated or inactivated by host and bacterial proteases commonly seen in the lungs of CF patients. If PAR are activated, it may be possible to develop antagonists which target specific PARS to modulate respiratory epithelial cell function. If inactivated, preservation by adjunct protease inhibitor treatment may be highly beneficial. We will use in vitro technology and cells derived from non-CF and CF patients. This study has great potential in the development of adjunct anti-inflammatory therapy for the treatment of both CF and other inflammatory lung diseases.Read moreRead less
THE ROLE OF UBIQUITIN LIGASE ADAPTOR PROTEIN NDFIP1 IN NEURONAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$581,813.00
Summary
Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UP ....Many brain diseases are characterized by faulty connections between nerve cells (neurons), in some cases caused by the inability to remove unwanted proteins from the neuron. This function is carried out by the ubiquitin-proteasome system (UPS). We have evidence that a UPS protein called Ndfip1 is important for forming functional brain circuits. We aim to discover whether neuron growth, branching and connectivity is promoted by Ndfip1 targeting of PTEN (phosphatase with tensin homology) to the UPS.Read moreRead less
Body Segment Identity Specification By The Transcription Regulator, Moz
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood ....One in 28 newborns have birth defects. Cleft palate and aortic arch defects are among the most common, always requiring surgery and often causing lethality. We propose to study a protein, Moz, which is essential for palate and aortic arch development. Moz (Monocytic leukaemia zinc finger protein) was first identified in human chromosomal abnormalities causing particularly aggressive forms of childhood and adult leukaemia. We have shown previously that Moz is essential for the formation of blood stem cells. Moz can regulate the activity of genes, but which genes it regulates in vivo is unknown. In the absence of Moz, mice are born with a cleft palate, lack the thymus, where immune cells are instructed, and fail to form the lung blood circulation, so that they are unable to supply their blood with oxygen after birth. Moz deficiency also causes defects of the vertebrate column, such that individual vertebrae acquire the appearance of their neighbours. These symptoms are typical for a general defect in positional information of individual body segments with respect to their location along the body axis. We will investigate the molecular mechanisms that require Moz in patterning of the body axis. This project will characterize a genetic mechanism that is crucial for normal development of the palate, the aorta and the vertebrate column.Read moreRead less
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$539,000.00
Summary
Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the ....Disorders of sexual development are among the most common forms of birth defects in humans (1 in 4,000 births). Many other childhood conditions with this incidence warrant prenatal diagnosis or neonatal screening. These disorders often result in infertility, genital abnormalities and gender mis-assignment. Uncertainty about a child s gender at birth can be very traumatic physically and psychologically for the individual and family concerned. There are profound consequences in later life for the affected individual. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research project will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans.Read moreRead less