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.
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.
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.
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
Dehumidification and cooling driven by solar/waste heat using liquid desiccants. The provision of comfort cooling is responsible for a considerable and increasing portion of the world energy demand and electricity peak demand. To substitute electrically driven vapour compression machines with their high electrical energy consumption and especially high peak loads, the use of solar energy or waste heat for a cooling and dehumidification system driven by liquid desiccants is a promising opportunit ....Dehumidification and cooling driven by solar/waste heat using liquid desiccants. The provision of comfort cooling is responsible for a considerable and increasing portion of the world energy demand and electricity peak demand. To substitute electrically driven vapour compression machines with their high electrical energy consumption and especially high peak loads, the use of solar energy or waste heat for a cooling and dehumidification system driven by liquid desiccants is a promising opportunity. The project utilises the complementary strengths in the research groups to develop practical and economically feasible cooling/dehumidification systems for different types of buildings with different moisture removal and cooling requirements at different locations (Australia, Southern Europe).Read moreRead less
A theoretical investigation into the effect of nonlinear wave interactions in promoting transition-to-turbulence. The problem of transition-to-turbulence remains one of the fundamental unanswered questions in fluid dynamics. An understanding of the processes leading to transition is necessary if the active control of turbulence is to be achieved. This project will focus attention on a new class of waves, which have only recently been described the CI, in order to determine how they are triggered ....A theoretical investigation into the effect of nonlinear wave interactions in promoting transition-to-turbulence. The problem of transition-to-turbulence remains one of the fundamental unanswered questions in fluid dynamics. An understanding of the processes leading to transition is necessary if the active control of turbulence is to be achieved. This project will focus attention on a new class of waves, which have only recently been described the CI, in order to determine how they are triggered and how they may serve to actively promote the early development of turbulence in a broad class of fluid flows.Read moreRead less
The effect of diffusive mass transfer on interfacial fluid instabilities. A wide variety of industrial and physiological fluid flows fall into the general class of two-layer fluids wherein a fluid of one density/viscosity flows over another of a different density/viscosity. Such flows can ultimately become turbulent (that is, chaotic) through the growth of small background disturbances. An understanding of this process is important in controlling fluid dynamical mixing. This project will conside ....The effect of diffusive mass transfer on interfacial fluid instabilities. A wide variety of industrial and physiological fluid flows fall into the general class of two-layer fluids wherein a fluid of one density/viscosity flows over another of a different density/viscosity. Such flows can ultimately become turbulent (that is, chaotic) through the growth of small background disturbances. An understanding of this process is important in controlling fluid dynamical mixing. This project will consider two layer flows in the case when diffusive mass transfer acts at the fluid interface with the aim of determining how diffusion affects the process of transition-to-turbulence.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0238345
Funder
Australian Research Council
Funding Amount
$373,000.00
Summary
Advanced Laser Diagnostics in Dilute Heterogeneous Combustion. This proposal seeks to establish a state-of-the-art laser diagnostics facility with unique capabilities for non-intrusive measurements in dilute multi-phase flows. Such heterogeneous flows which involve stationary surfaces, disperse suspended droplets or suspended particles are found in many applications including engines, furnaces, industrial and chemical processing and micro-combustion devices. This facility will give Australian re ....Advanced Laser Diagnostics in Dilute Heterogeneous Combustion. This proposal seeks to establish a state-of-the-art laser diagnostics facility with unique capabilities for non-intrusive measurements in dilute multi-phase flows. Such heterogeneous flows which involve stationary surfaces, disperse suspended droplets or suspended particles are found in many applications including engines, furnaces, industrial and chemical processing and micro-combustion devices. This facility will give Australian researchers the unprecedented opportunity to perform measurements of flow, mixing, temperature and composition fields in the gas and liquid or solid phases simultaneously. The resulting data will advance current knowledge in these complex flows and lead to new and improved reactor designs.
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