Sclerostin: A Key Regulator Of Bone Mineralisation And Bone Catabolism
Funder
National Health and Medical Research Council
Funding Amount
$536,653.00
Summary
The regulation of bone mass is critical for many areas of human disease including osteoporosis, osteoarthritis, inflammatory bone loss conditions, e.g. rheumatoid arthritis, cancers of bone and problems relating to orthopaedic prosthesis failure. The osteocyte, the most abundant bone cell, plays a central role in normal bone biology and is likely key to these diseases. Sclerostin is one osteocyte product that may be a key to understanding how boneÍs mass and composition is controlled locally.
The Role Of Growth Factors In Pluripotency And Differentiation Of Human Embryonic Stem Cells Towards Human Therapy
Funder
National Health and Medical Research Council
Funding Amount
$380,829.00
Summary
Human stem cells, obtained and studied within strict ethical guidelines, have huge potential for increasing our understanding of early human development and for transplantation therapy. In order to realise this potential the factors that maintain these cells as stem cells (able to divide indefinitely and to become any cell type) and which turn them into particular cell types must be understood. This project aims to study these factors and to apply stem cells to muscle disease therapy.
Investigation Of Delta3 Function And Notch Signalling During Cell Fate Specification In Mouse And Human
Funder
National Health and Medical Research Council
Funding Amount
$221,717.00
Summary
This project seeks to understand how cells within the developing embryo are produced and how they are given a specific identity. These processes often require the cell to make a decision about what type of cell it will become. We are using the Delta3 gene, which is present in humans and in the mouse, as a tool for our investigations. Delta3 is expressed at the surface of the cell and Notch (its receptor) is present on the surface of neighbouring cells. Delta3 on one cell will bind to Notch on th ....This project seeks to understand how cells within the developing embryo are produced and how they are given a specific identity. These processes often require the cell to make a decision about what type of cell it will become. We are using the Delta3 gene, which is present in humans and in the mouse, as a tool for our investigations. Delta3 is expressed at the surface of the cell and Notch (its receptor) is present on the surface of neighbouring cells. Delta3 on one cell will bind to Notch on the neighbouring cell and activates Notch. When Notch is activated in a cell it pushes the cell to make its decision. This project aims to determine what exactly is the function of Delta3 in mammals and how at the level of the individual cell this protein exerts its effects. We have generated a mouse in which the Delta3 gene is no longer active and have observed that embryos do not develop normally. We will explore these defects (which affect the skeleton and the brain) in detail in order to define their origins. We will also use these abnormal mice to identify genes, which require the function of Delta3 for their normal activity. It is not only important to define the function of Delta3 in mammals but also to determine this protein functions. We wish to know how exactly Delta3 interacts with Notch. That is, which part of the Delta3 protein binds to which part of the Notch protein. We can address this by modifying the Delta3 protein in small (but revealing ways) and see if it can still bind the Notch receptor in a cell culture assay. Our studies have relevance to humans because recently it has been shown that Delta and Notch are associated with a human syndrome (spondylocostal dysostosis) in which individuals suffer from abnormal skeletons.Read moreRead less
THE ROLE OF RESIDENT MAST CELLS IN ISCHAEMIA-REPERFUSION INJURY OF SKELETAL MUSCLE.
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the blood-oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected to more injury, which is thought to be caused by oxygen and-or white blood cells. This type of injury occurs in muscle which has been crushed, limbs that have been broken or traumatized, in ....NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the blood-oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected to more injury, which is thought to be caused by oxygen and-or white blood cells. This type of injury occurs in muscle which has been crushed, limbs that have been broken or traumatized, in replantation of amputated parts, in transplantation, after some surgical procedures and after microsurgical transfer of muscle. Once established there is no effective treatment. Our experiments show that a particular cell, the mast cell, and a particular molecule, nitric oxide, are involved in causing ischaemia reperfusion injury. However, the extent of their involvement is unknown. In this proposal we will investigate the effect of replacing mast cells into muscles, in a unique variety of mice which normally don t contain mast cells and are resistant to ischaemia reperfusion injury. In one group of mice we will put back normal mast cells and in a second group of mice we will put back mast cells that cannot produce the nitric oxide molecule. These experiments will determine, unambiguously, the extent of involvement of mast cells and mast cell-derived nitric oxide. In the second part of this proposal will carry out a time course study, using pharmacologically induced mast cell degranulation, to determine when the mast cells become injurious to skeletal muscle. These experiments will identify the period during which mast cell behaviour can be modulated in order to protect the muscle from ischaemia reperfusion injury. Determination of the role of mast cells, and an understanding of the timing during which they become injurious would provide a logical basis for optimizing drug therapy in clinical applications of these findings.Read moreRead less
Switching the light on cartilage repair. Osteoarthritis is a leading cause of pain and disability in adults and affects 15 per cent of the Australian population. This project will develop a revolutionary new approach to treat joint disorders using smart materials and stem cells. The novel materials and techniques developed will help Australia maintain its leading edge in biotechnology.
Establishing STARS As A Therapeutic Target To Reduce Muscle Wasting And Improve Muscle Function
Funder
National Health and Medical Research Council
Funding Amount
$446,189.00
Summary
Muscle wasting occurs rapidly with disuse after injuries occurring at work, during sport, with chronic disease and in road accidents. It is also a consequence of ageing. Muscle wasting and reduced muscle function places considerable financial strain on our health care system. We aim to use gene therapy and pharmacological interventions to increase the levels of a protein called STARS. We hypothesize that STARS will reduce disuse-induced muscle wasting, increase recovery and improve function.
Using Gene Delivery Technologies To Define Novel Mechanisms Of Skeletal Muscle Adaptation, And Develop Muscle-directed Interventions For Frailty And Serious Illness
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and disease. By defining these processes we can establish the events contributing to muscle wasting and frailty commonly associated with serious illness and advancing age, and develop interventions to prevent/overcome this important contributor to poor health prospects and reduced survival.
Industrial Transformation Training Centres - Grant ID: IC170100022
Funder
Australian Research Council
Funding Amount
$4,420,408.00
Summary
ARC Training Centre for Innovative BioEngineering. The ARC Training Centre for Musculoskeletal Biomedical Technologies will provide the next-generation of skilled graduates to overcome industry-focused challenges in musculoskeletal regeneration. The Centre expects to engineer a set of integrated technologies to personalise implants for the unique biological, physical and lifestyle characteristics of the recipient. Expected outcomes of the Centre include embedded bioelectronic sensors to assess a ....ARC Training Centre for Innovative BioEngineering. The ARC Training Centre for Musculoskeletal Biomedical Technologies will provide the next-generation of skilled graduates to overcome industry-focused challenges in musculoskeletal regeneration. The Centre expects to engineer a set of integrated technologies to personalise implants for the unique biological, physical and lifestyle characteristics of the recipient. Expected outcomes of the Centre include embedded bioelectronic sensors to assess and optimise the healing process. In addition, the Centre will produce data for use in deriving the next-generation of implants, giving rise to improved health outcomes, economic benefits, and a skilled workforce able to advance and perpetuate this important field.Read moreRead less
Novel Approach And Insights Into Muscle Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$642,401.00
Summary
The successful use of stem cell therapy absolutely requires the longterm intergration of the therapeutic cells into the target tissue. This application will adapt a chemotherapy-based strategy to drive the successful incorporation and growth of healthy muscle stem cells into diseased muscle. This study will both enhance our understanding of muscle stem cells and provide proof-of-principle for a universal approach to the uptake of stem cells by a target tissue.