Significance Of Low-level Mosaicism To Intellectual Disability In Paediatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$483,402.00
Summary
My vision for the next 4 years is to improve outcomes for children and their families with inherited disorders associated with intellectual disability (ID) and autism through earlier diagnosis and intervention. This is of great importance with annual costs of ID close $14.72 billion to the Australian health system, and missed or delayed diagnoses being a significant problem, as ID is found in 1.7% of births, where a specific cause is currently identified in less than half.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
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.
Mechanism Of Anoxic Iron Acquisition In Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$536,280.00
Summary
All organisms require iron for their survival, including all bacterial species. Bacterial pathogens growing in anaerobic environments, such as in our gut, gum, or tissue, sequester iron through the divalent iron transporter FeoB. We aim to divulge the mechanism of iron transport through FeoB by structural and functional studies, and thus provide a scaffold for a non-conventional antimicrobial target.
Erythroid Molecular Cascades Involving The Tyrosine Kinase Lyn
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functio ....Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. Recently, we have demonstrated that mice lacking the Lyn gene develope major problems with their red blood cells. We have identified several molecules which interact with Lyn in red blood cells. We have shown that a molecule called Cbp is important for Epo function in individual red blood cells and now we plan to investigate its function in whole animals. We have shown that a new molecule called Arp is important for red blood cell development. This protein moves in and out of the nucleus (where DNA is stored) and may be important in the regulation of genes needed for red blood cells. The third gene (AFAPbeta) is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Since red blood cells have to shrink considerably during their development, the role of AFAPbeta on red blood cell structure will also be investigated. From these experiments we should develop a much better understanding of how the production of red blood cells is controlled and how diseases of red blood cells (such as anaemia) occur.Read moreRead less
Characterising The Beta-catenin Nuclear Targeting Pathway In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$485,081.00
Summary
Bowel cancer is caused by inherited gene mutations that cause build-up of beta-catenin protein in the cell nucleus. Bowel cancer is the second largest cause of cancer deaths in Australia. We aim to study the mechanisms controlling beta-catenin accumulation in the nucleus. We will characterise new signalling pathways that control movement and activity of beta-catenin in the nucleus. This will yield insights into the role of beta-catenin in cancer and possible targets for therapy.
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Identification And Characterisation Of Novel Genes For Congenital Cataract
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Au ....Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.Read moreRead less
Implementation Of A New, Inexpensive And High-throughput Matrix Assisted Laser Desorption / Ionization _ Time Of Flight Mass Spectrometry Test For Superior Detection Of Fragile X Syndrome In Targeted Diagnostics And Newborn Population Screening.
Funder
National Health and Medical Research Council
Funding Amount
$254,175.00
Summary
Background: The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability. There are now a number of treatments for FXS. However, often this disorder is not clearly recognized. We have developed a novel FXS test that could resolve this issue. Our objective is to develop a commercial package that describes suitability of our test for diagnostic use. If successful this could potentially leading to improvement in the prognosis for FXS children through early treatment int ....Background: The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability. There are now a number of treatments for FXS. However, often this disorder is not clearly recognized. We have developed a novel FXS test that could resolve this issue. Our objective is to develop a commercial package that describes suitability of our test for diagnostic use. If successful this could potentially leading to improvement in the prognosis for FXS children through early treatment intervention.Read moreRead less
Characterization Of A Novel Epigenetic Boundary And Long Range Epigenetic Modifications Specific To FMR1 Expansion Carriers With Behavioural And Cognitive Disorders - Implications For Earlier Diagnosis And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$670,836.00
Summary
Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and autism and is caused by a faulty switch in the gene FMR1. We have discovered new DNA regions important in FXS. The project aims to explain how these new regions regulate the FMR1 gene. This is essential for the discovery and validation of new avenues for earlier diagnosis, treatments and therapies for children and adults with FMR1 disorders and also for informing reproductive decisions.