Mechanisms Of Premature Cranial Fusion: Role Of Retinol Binding Protein 4 In Osteogenesis And Suture Fusion
Funder
National Health and Medical Research Council
Funding Amount
$555,855.00
Summary
Craniosynostosis is a condition where the skull bones fuse prematurely, affecting skull shape, vision and cognition. It occurs in 1 in 2,500 births. The only treatment is surgery, which is life-threatening, costly and may need to be repeated. By studying how fusion happens in this project we may be able to devise therapies to minimize the risks and need for re-operation. Here, we hope to show that modification of a single substance in the skull of mouse models can prevent premature bone fusion.
Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately exp ....We will seek to address an important clinical problem in orthpaedics, namely the bone loss that commonly occurs around joint replacement prostheses. Termed peri-prosthetic osteolysis (PO), this bone loss can result in the loosening and ultimate failure and need for revision of the artificial joint components. PO is thought to be caused by the body's reaction to wear particles generated from the articulating surface of the prosthesis. However, it has not previously been possible to accurately explore the relationship between prothesis wear and PO, or the progression of PO, because of a lack of techniques to image and measure the volume of PO around metal prosthesis components. We have developed a means to accurately and reproducibly measure the volume of bone loss, using CT, and will do so longitudinally in joint replacement patients to obtain the first information about the progression of PO. New computer based methods will be used concurrently to relate prosthesis wear and migration parameters to PO. Patients who come to surgery for replacement of failed prostheses will be investigated further by analysis of the tissues involved in the bone loss around prostheses. Basic science experiments will seek to understand the underlying causes of PO and the findings will be important in interpreting the clinical results. An animal model will be used to seek approaches to inhibiting the pathological response to wear particles. The significance of these studies is that they will lead to improved outcomes for joint replacement patients, increasing the interval to revision surgery, which is both extremely costly and brings an attendant morbidity and mortality.Read moreRead less
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100028
Funder
Australian Research Council
Funding Amount
$3,000,000.00
Summary
Australian Membership of the International Ocean Discovery Program. This proposal is for an 18-month membership of the International Ocean Discovery Program (IODP), the world’s largest collaborative research program in Earth and Ocean sciences. The Program studies the history and current activity of the Earth by conducting seagoing coring expeditions and monitoring of instrumented boreholes, using globally unique infrastructure that Australians would otherwise have no access to. Program outcomes ....Australian Membership of the International Ocean Discovery Program. This proposal is for an 18-month membership of the International Ocean Discovery Program (IODP), the world’s largest collaborative research program in Earth and Ocean sciences. The Program studies the history and current activity of the Earth by conducting seagoing coring expeditions and monitoring of instrumented boreholes, using globally unique infrastructure that Australians would otherwise have no access to. Program outcomes include understanding past global environmental change on multiple time scales, the deep biosphere, plate tectonics, formation and distribution of resources, and generation of hazards. These outcomes are paramount to Australia’s national science and research priorities, and societal and economic prosperity.Read moreRead less
The application of clumped isotope thermometry to the terrestrial environment. Clumped-isotope geochemistry, a novel method for measuring the temperature of formation of carbonate minerals, will be applied to terrestrial materials (soil carbonates, lake deposits and speleothems) from Australia and New Zealand. The method relates the abundance or 'clumping' of rare isotopes (for example, carbon dioxide of mass 47 as carbon-13, oxygen-18, oxygen-16) extracted from carbonates to their formation tem ....The application of clumped isotope thermometry to the terrestrial environment. Clumped-isotope geochemistry, a novel method for measuring the temperature of formation of carbonate minerals, will be applied to terrestrial materials (soil carbonates, lake deposits and speleothems) from Australia and New Zealand. The method relates the abundance or 'clumping' of rare isotopes (for example, carbon dioxide of mass 47 as carbon-13, oxygen-18, oxygen-16) extracted from carbonates to their formation temperature and is independent of the oxygen-18:oxygen-16 value of the host water from which the mineral precipitated. The materials to be investigated span the Last Glacial-Interglacial Transition and will provide robust past temperature estimates and the delta-oxygen-18 values of waters, thereby permitting hydrological balances (for example, precipitation/evaporation) to be constructed. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100067
Funder
Australian Research Council
Funding Amount
$10,000,000.00
Summary
Australian Membership of the International Ocean Discovery Program. Australian membership of the International Ocean Discovery Program:
This project is for a 5-year membership of the International Ocean Discovery Program, the world’s largest collaborative research program in earth and ocean sciences addressing international priorities. The program conducts seagoing coring expeditions and monitoring of instrumented boreholes to study the history and current activity of the Earth, recorded in sed ....Australian Membership of the International Ocean Discovery Program. Australian membership of the International Ocean Discovery Program:
This project is for a 5-year membership of the International Ocean Discovery Program, the world’s largest collaborative research program in earth and ocean sciences addressing international priorities. The program conducts seagoing coring expeditions and monitoring of instrumented boreholes to study the history and current activity of the Earth, recorded in sediments and rocks below the seafloor. The program’s aims include understanding past global environments on multiple time scales, the deep biosphere, plate tectonics, occurrence and distribution of resources, and generation of hazards. Several multinational expeditions are scheduled and planned in our marine jurisdiction and within the Australasian region. Read moreRead less
Dead Heart Beating? Landscape, Climate and People in Desert Australia. This project aims to undertake the first detailed investigation of the archaeology, landscape history and paleoenvironment of dryland lakes in the Simpson, Strzelecki and Stuart Stony Deserts in Central Australia. Using cutting edge methods, the project expects to discover new archaeological sites, provide a new climate record for inland Australia and develop innovative new analytical and field techniques. Expected benefits a ....Dead Heart Beating? Landscape, Climate and People in Desert Australia. This project aims to undertake the first detailed investigation of the archaeology, landscape history and paleoenvironment of dryland lakes in the Simpson, Strzelecki and Stuart Stony Deserts in Central Australia. Using cutting edge methods, the project expects to discover new archaeological sites, provide a new climate record for inland Australia and develop innovative new analytical and field techniques. Expected benefits also include the development of new cutting-edge methodologies for the investigation of Australian desert landscapes, comprehensive baseline data of how this region has evolved prior to European colonization and resolving why no Pleistocene aged archaeological sites have been found in the region.Read moreRead less
Special Research Initiatives - Grant ID: SR200100008
Funder
Australian Research Council
Funding Amount
$20,000,000.00
Summary
The Australian Centre for Excellence in Antarctic Science. The Centre will revolutionise predictions of the future of East Antarctica and the Southern Ocean. Changes in the Antarctic will be profoundly costly to Australia, including sea-level and fisheries impacts; but the speed and scale of future change remains poorly understood. A new national-scale and interdisciplinary Centre is required to understand the complex interactions of the ocean, ice sheets, atmosphere and ecosystems that will gov ....The Australian Centre for Excellence in Antarctic Science. The Centre will revolutionise predictions of the future of East Antarctica and the Southern Ocean. Changes in the Antarctic will be profoundly costly to Australia, including sea-level and fisheries impacts; but the speed and scale of future change remains poorly understood. A new national-scale and interdisciplinary Centre is required to understand the complex interactions of the ocean, ice sheets, atmosphere and ecosystems that will govern Antarctica’s future. The Centre will combine new field data with innovative models to address Australia’s Antarctic science priorities, train graduate students, develop leaders, engage the public, and enable major economic benefit as Australia adapts to climate change in the coming years and beyond.Read moreRead less