Novel Fragile X Syndrome Prevalence Estimates In 100,000 Australian Newborns, Prognostic And Health-economic Outcomes: A Retrospective Newborn Screening Study
Funder
National Health and Medical Research Council
Funding Amount
$769,866.00
Summary
Fragile X syndrome (FXS) is a common heritable cause of intellectual disability and co-morbid autism, caused by epigenetic silencing of the FMR1 gene. This will be the world’s largest FXS mutation prevalence study conducted in 100,000 newborns using a novel test targeting epigenetic changes, and will also explore the prognostic outcomes, costs and benefits associated with FXS newborn screening, providing conclusions regarding expanding the current newborn screening in Australia to include FXS.
Communication Disabilities And Patient Safety In Hospital.
Funder
National Health and Medical Research Council
Funding Amount
$341,111.00
Summary
Hospital patients with communication disabilities are up to three times more likely than other patients to experience preventable, harmful patient safety incidents. We will develop (a) a theoretically sound and evidence based framework that helps to prevent and manage patient safety incidents, and (b) a Clinical Audit Tool for Communication in Hospital (CATCH) to improve patient safety for adults with little or no speech. This information will reduce costs associated with adverse events, and imp ....Hospital patients with communication disabilities are up to three times more likely than other patients to experience preventable, harmful patient safety incidents. We will develop (a) a theoretically sound and evidence based framework that helps to prevent and manage patient safety incidents, and (b) a Clinical Audit Tool for Communication in Hospital (CATCH) to improve patient safety for adults with little or no speech. This information will reduce costs associated with adverse events, and improve patient care.Read moreRead less
Ciliopathies are an emerging group of syndromes in society that have devastating health effects. Ciliopathy patients exhibit a specturm of disorders including polycystic kidneys, extra digits, retinal degeneration and neural tube defects. INPP5E is a gene that is mutated in patients with a ciliopathy syndrome. These studies will determine the role of INPP5E in ciliopathy disease and may identify INPP5E as a novel treatment target.
The Identification Of Genes Involved In Mammalian Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
Birth defects arising from abnormal development of the embryo are a major cause of infant mortality and childhood disabilities. On average 3-4% of liveborn babies have a major congenital abnormality, and of the 15-20% of pregnancies which spontaneously abort, many are due to chromosomal or other developmental anomalies. A common feature of many developmental disorders is dysmorphology of the face, suggesting that genes important in patterning the face are also important in the development of oth ....Birth defects arising from abnormal development of the embryo are a major cause of infant mortality and childhood disabilities. On average 3-4% of liveborn babies have a major congenital abnormality, and of the 15-20% of pregnancies which spontaneously abort, many are due to chromosomal or other developmental anomalies. A common feature of many developmental disorders is dysmorphology of the face, suggesting that genes important in patterning the face are also important in the development of other organ systems. During development of the embryo many of the features of the face derive from a series of swellings termed the pharyngeal arches. The complex processes which determine how the face develops are in a large part controlled by the co-ordinated expression of a large number of genes in the first two of the five pharyngeal arch pairs. While we know some of the genes involved in these processes, the precise mechanisms of craniofacial development are relatively poorly understood. In this project we propose a large scale approach to identifying genes involved in development of the mammalian face and to further delineating their role in development and human disease. This approach takes advantage of state of the art genomic technologies available at the IMB and through existing collaborations overseas. In collaboration with Dr Bento Soares (University of Iowa) we have constructed a library containing all of the genes which are expressed in the first two pairs of pharyngeal arches in the developing mouse embryo. Using an approach designed to eliminate all those genes which are expressed in all or most tissues of the body and play a general role in the body's metabolism, we will select for those genes which play a specific and important role in embryonic development. We will then isolate the human counterparts of these genes and more thoroughly investigate their role in embryonic development and disease.Read moreRead less
A New Paradigm For SWI/SNF Chromatin Function; The ATPase Dependent Remodeler Is A Component Of The MeCP2 Complex
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
DNA methylation is a major determinant in the epigenetic silencing of many genes. The mechanisms underlying that targeting of DNA methylation and the consequence, that is, transcriptional silencing are relevant to human development and disease. Examples of the significance of alterations in the controls of DNA methylation and histone deacetylation in human disease include mental retardation (fragile X syndrome, Rett syndrome) and carcinogenesis. Evidence is emerging that a family of methylation ....DNA methylation is a major determinant in the epigenetic silencing of many genes. The mechanisms underlying that targeting of DNA methylation and the consequence, that is, transcriptional silencing are relevant to human development and disease. Examples of the significance of alterations in the controls of DNA methylation and histone deacetylation in human disease include mental retardation (fragile X syndrome, Rett syndrome) and carcinogenesis. Evidence is emerging that a family of methylation specific (methyl-CpG binding domain, MBD) proteins have the capacity to bind to methylated sequences and repress transcription. The mechanisms that target CpG methylation however still remain unclear. Furthermore, it is becoming increasingly evident that methyl-CpG binding proteins are not alone in silencing transcription and other epigenetic components are thought to influence transcription (namely, SWI-SNF activation complex). This grant proposal concentrates on our most recent work which demonstrates a new molecular mechanism of transcriptional repression extending the mechanism mediated by MeCP2. Our results are the first to show that the human SWI-SNF ATPase complex is a transcriptional repressor and is identified as part of the MeCP2-histone deacetylase repressor complex. This data extends the mechanistic link between DNA methylation, chromatin remodelling and transcriptional regulation. More importantly, the experimental findings could lead to a re-examination of the mechanistic basis behind MeCP2 transcriptional repression and epigenetic modification. Our findings suggest a new paradigm for SWI-SNF as a component of the MeCP2 methylation dependent silencing complex.Read moreRead less
Urine Proteomics As A New Diagnostic Approach For Cardiovascular Risk And As A Discovery Tool For Novel Pathomechanisms In Atherosclerotic Disease
Funder
National Health and Medical Research Council
Funding Amount
$69,500.00
Summary
Atherosclerosis (hardening of blood vessels) followed by blockage is the leading cause of death due to heart attacks and strokes. Up until now there has been no simple tests to predict this reliably.The outcome of this project will give us a better understanding of atherosclerosis and provide a simple non-invasive urine test to detect atherosclerosis which would lend clinicians the opportunity to intervene early.
Evaluation Of Optimal Pharmacologic Haemodynamic Support Strategies In Patients Presenting With Shock
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Shock is one of the most challenging clinical management scenarios experienced by clinicians. It is a syndrome characterised by an imbalance of oxygen delivery and demand particularly in vital organs. Despite the advances in current treatment strategies for patients with shock, there is still significant morbidity and mortality associated with this syndrome. It is the goal of my PhD to develop improved treatment pathways for patients with shock in order to improve their clinical outcomes.
Centre Of Excellence For Clinical Research Training In Translational Cardiology
Funder
National Health and Medical Research Council
Funding Amount
$2,622,253.00
Summary
We aim to convert novel scientific findings to better treating patients with end-stage heart disease. A secondary aim is to train clinicians with a better understanding of sophisticated scientific approaches so they can better transfer this knowledge to health practices and policies. We will study new ways of identifying patients who are likely to suffer from heart attacks as well as those with heart problems who appear to function well but in fact have poor health and life outlook.
Optimizing Evidence Translation In The High-risk Time-critical Environment Of The Emergency Management For Suspected Cardiac Chest Pain (RAPIDx)
Funder
National Health and Medical Research Council
Funding Amount
$1,230,191.00
Summary
Few clinical processes are purposefully redesigned to optimally incorporate new diagnostic test into routine practice. Using artificial intelligence to enhance the interpretation of newly identified troponin elevation with high sensitivity troponin assays, we will implement a myocardial injury registry in practice. It will also form a platform to explore the clinical impact of artificial intelligence, through a cluster randomized trial evaluating decision-support on 12-month outcomes.
The Role Of New Generation Multidetector Row CT For Identification And Management Of Vulnerable Plaque At Risk Of Acute Coronary Syndrome : A Prospective Observational And Interventional Study
Funder
National Health and Medical Research Council
Funding Amount
$189,326.00
Summary
Heart attack remains one of the major cause of death. This is usually due to rupture of a plaque (due to cholesterol buildup) in the major heart arteries. Studies using invasive ultrasound have identified some features of plaque that are at high risk of rupture. These plaques are referred to as "vulnerable plaque". Recent developments in the computed tomography (CT) technology which is a non-invasive technique has enabled us to also identify these features. However thus far, no prospective large