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.
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
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.
Meals on Wheels: building towards a new social experiment for our times. This project contributes directly to the National Research Priority, promoting and maintaining good health: ageing well, ageing productively, through developing evidence-based knowledge on which to build future volunteer business models. With the rapid ageing of the Australian population, it is imperative that volunteer-based organisations, such as Meals on Wheels, innovate to continue to deliver essential community service ....Meals on Wheels: building towards a new social experiment for our times. This project contributes directly to the National Research Priority, promoting and maintaining good health: ageing well, ageing productively, through developing evidence-based knowledge on which to build future volunteer business models. With the rapid ageing of the Australian population, it is imperative that volunteer-based organisations, such as Meals on Wheels, innovate to continue to deliver essential community services in a sustainable and cost-effective way. Meals on Wheels is integral within community care for frail, older people and those with disabilities, keeping people in their own homes and out of institutional care. Using national and international examples, the research has the potential to be adopted by the broad community services sector in Australia.Read moreRead less
Confronting everyday harms: preventing abuse of people with disability. The findings of the Disability Royal Commission necessitate new approaches to prevent violence, abuse, neglect and exploitation. Framed by recognition theory, this project proposes empirical research with young people with cognitive disability, using a new concept of ‘everyday harms’ in their paid relationships. The results will inform early responses to poor quality interactions in disability support. The strategic alliance ....Confronting everyday harms: preventing abuse of people with disability. The findings of the Disability Royal Commission necessitate new approaches to prevent violence, abuse, neglect and exploitation. Framed by recognition theory, this project proposes empirical research with young people with cognitive disability, using a new concept of ‘everyday harms’ in their paid relationships. The results will inform early responses to poor quality interactions in disability support. The strategic alliances with the government, industry and community partners will develop a practice framework to prevent everyday harms and the escalation to abuse, and to promote safety and wellbeing. The research has policy benefits for capacity-building in the sector to act on the rights and voices of people with disability. Read moreRead less
Young people with cognitive disability: relationships and paid support. This project aims to improve the rights and wellbeing of young people with cognitive disability by exploring their relationship and interaction with paid support workers. The introduction of national individualised funding and support is a watershed in Australian disability policy. Understanding the role that paid support plays in the ongoing identity development of these young people is urgently needed to realise national p ....Young people with cognitive disability: relationships and paid support. This project aims to improve the rights and wellbeing of young people with cognitive disability by exploring their relationship and interaction with paid support workers. The introduction of national individualised funding and support is a watershed in Australian disability policy. Understanding the role that paid support plays in the ongoing identity development of these young people is urgently needed to realise national policy aspirations for people with disability of rights, choice, inclusion and independence. Using social geography and recognition theory, the project expects to deliver new understanding and improved practice around how paid support relationships can foster mutual care, respect and value at a critically important time in young people’s lives.Read moreRead less
The nature, extent and effect of infant removal by child protection. This project aims to provide new knowledge about the nature, extent and effect of removals of babies from their parents in Australia. Removal is the highest level of intervention by the child protection system, and one which some mothers experienced on multiple occasions. Little is known, however, about its incidence and effects, nor whether there are over-represented groups (e.g. Aboriginal mothers and babies) who would respon ....The nature, extent and effect of infant removal by child protection. This project aims to provide new knowledge about the nature, extent and effect of removals of babies from their parents in Australia. Removal is the highest level of intervention by the child protection system, and one which some mothers experienced on multiple occasions. Little is known, however, about its incidence and effects, nor whether there are over-represented groups (e.g. Aboriginal mothers and babies) who would respond to targeted interventions. This project aims to identify appropriate early intervention and prevention strategies, preventing the need for babies to spend their whole childhood in care at great financial and societal cost.Read moreRead less