Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approache ....Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approaches for developing stem cell therapies and the production of novel biomaterials for the repair of bones and joints. The outcomes of this study will therefore benefit the full spectrum of society from infants to the aged.Read moreRead less
Angiogenic defects in mutant growth plate cartilage reveal new modulators of vascular invasion. Converting cartilage to bone requires blood vessel invasion from the bony interface. This project will test, in vitro and in vivo, the hypothesis that collagen fragments regulate blood vessel invasion into cartilage. This data will have implications for processes requiring new blood vessels such as bone growth, cancer, inflammation and ischemia.
Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development a ....Proteomic and Transcriptional Profiling of Cartilage. Gene expression and signalling pathways that regulate cartilage formation, and its orderly transition to bone, are poorly described. Our studies will, for the first time, combine two complementary cutting-edge approaches, protein identification by proteomic analysis, and mRNA profiling by microarray analysis, to define these pathways and develop a comprehensive catalogue of proteins and gene expression patterns during cartilage development and bone formation. This information will provide insight into the regulation of cartilage differentiation, maturation and structure, and will provide a critical platform for the development of more sophisticated cartilage and bone biomaterials for improved tissue repair and regeneration.Read moreRead less
Numerical investigation of signal mechanotransduction of bone cells - application to bone remodeling. The understanding of signal mechanotransduction of bone cells is directly related to mechanical activation of bone remodeling processes, i.e., resorption and formation of bone tissue. Understanding of bone remodeling is essential for the development of new bone implants, the prognosis of osteosporosis, and studies related to changes in microgravity (e.g. space flight) to name a few key applicati ....Numerical investigation of signal mechanotransduction of bone cells - application to bone remodeling. The understanding of signal mechanotransduction of bone cells is directly related to mechanical activation of bone remodeling processes, i.e., resorption and formation of bone tissue. Understanding of bone remodeling is essential for the development of new bone implants, the prognosis of osteosporosis, and studies related to changes in microgravity (e.g. space flight) to name a few key applications. This research proposal closely aligns with one of the major national research priorities, i.e., promoting and maintaining good health (ageing well, ageing productively). The research project is aimed to understand how mechanically induced loading may activate remodeling of bone.
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Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the ....Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the necessary interdisciplinary approach to generate a new product for patients in need of bone regeneration. Australia will benefit from the contribution to medical science, the development of a new device for rapid prototyping tissue engineering scaffolds, retain biomaterials research expertise, and generate new biomedical products.Read moreRead less
Multi-scale modeling of transport through deformable porous materials. Understanding solute transport through porous materials is essential because it provides a technical basis for answering many important questions in society today-how can humans avoid 'brittle bones', how to design durable infrastructure, how to safely store wastes (e.g. hazardous and municipal). Solution of each of these problems requires innovation in model development, new method of analysis, and insightful interpretation ....Multi-scale modeling of transport through deformable porous materials. Understanding solute transport through porous materials is essential because it provides a technical basis for answering many important questions in society today-how can humans avoid 'brittle bones', how to design durable infrastructure, how to safely store wastes (e.g. hazardous and municipal). Solution of each of these problems requires innovation in model development, new method of analysis, and insightful interpretation of results. While theoretical developments of this project are general, in the sense that they are not restricted to particular engineering disciplines, the four chosen applications closely align with two major research priorities namely An Environmental Sustainable Australia and Promoting and Maintaining Good Health.Read moreRead less
Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine ....Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine how evolution works at the DNA level. This proposal will determine if animals that develop identical skull shapes, also show identical changes in their DNA. The findings will define new developmental genes and explain how selection, adaptation and evolution works at the DNA level. Read moreRead less
Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.
Bone regulation - cell interactions to disease. Many bone disorders such as osteoporosis, Paget's disease and chancer related bone diseases are directly related to disruption of communication pathways between bone cells leading to imbalances in bone remodeling. Although these disorders are common and cause considerable suffering, in most cases little is known about the mechanisms responsible for dysfunctional remodeling. Understanding the communication network between bone cells and their inter ....Bone regulation - cell interactions to disease. Many bone disorders such as osteoporosis, Paget's disease and chancer related bone diseases are directly related to disruption of communication pathways between bone cells leading to imbalances in bone remodeling. Although these disorders are common and cause considerable suffering, in most cases little is known about the mechanisms responsible for dysfunctional remodeling. Understanding the communication network between bone cells and their interaction with drugs is essential in order to develop new therapies and to effectively design novel biological compatible bone implants. This research proposal closely aligns with national research priority two, i.e., promoting and maintaining good health (ageing well, ageing productively).Read moreRead less
Engineering cartilage homeostasis in health and disease. Arthritis is a common, painful and often debilitating disease affecting 16% of the Australian population and costing this community $11 billion every year. It is not well understood why cartilage degenerates into joint disease, nor how it may be reversed - partly due to the large number of mechanisms involved. This project aims to overcome this complexity by developing a computational model of cartilage that can integrate the various mech ....Engineering cartilage homeostasis in health and disease. Arthritis is a common, painful and often debilitating disease affecting 16% of the Australian population and costing this community $11 billion every year. It is not well understood why cartilage degenerates into joint disease, nor how it may be reversed - partly due to the large number of mechanisms involved. This project aims to overcome this complexity by developing a computational model of cartilage that can integrate the various mechanisms of cartilage degradation. New experiments will be used to validate the model and test predictions. The model developed will provide fundamental insights into what is required for the maintenance of healthy cartilage, and what happens in injury-induced degradation of cartilage.Read moreRead less