The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
Mitochondrially targeted anti-cancer drugs modulate the mitochondrial genome. Successful cancer management requires novel therapeutical approaches. This project will test the effect of a new class of compounds that target mitochondria, the powerhouse of the cells, where they suppress expression of mitochondrial genes. By this mechanism, cancers that are resistant to apoptosis induction can be inhibited.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Participation following traumatic brain injury in rural, regional and remote areas. The results of this project will lead to improved rehabilitation programs and better outcomes for people with brain injury, especially in regional, rural and remote areas, by targeting the ultimate goal more directly: participation - getting people back into their home, work and community roles. Participation is associated with improved social networks, wellbeing, independence and quality of life, so health care ....Participation following traumatic brain injury in rural, regional and remote areas. The results of this project will lead to improved rehabilitation programs and better outcomes for people with brain injury, especially in regional, rural and remote areas, by targeting the ultimate goal more directly: participation - getting people back into their home, work and community roles. Participation is associated with improved social networks, wellbeing, independence and quality of life, so health care burdens and costs are reduced, and people can lead more productive lives. The project's emphasis on country areas will benefit rural health care, and also help specialist metropolitan brain injury services to understand the specific rehabilitation issues facing people from the bush.Read moreRead less
Gene therapy to enhance auditory prosthesis performance for cochlear implants. The cochlear implant is the most effective neural prosthesis, restoring hearing to the deaf. The research aims to develop a new type of implant compatible with delivery of therapeutic genes to the cells lining the cochlea. Gene therapy DNA constructs will be developed that will enhance neural survival and growth, improving cochlear implant performance. The research will provide advances in understanding how to tran ....Gene therapy to enhance auditory prosthesis performance for cochlear implants. The cochlear implant is the most effective neural prosthesis, restoring hearing to the deaf. The research aims to develop a new type of implant compatible with delivery of therapeutic genes to the cells lining the cochlea. Gene therapy DNA constructs will be developed that will enhance neural survival and growth, improving cochlear implant performance. The research will provide advances in understanding how to transfer genes into cochlear tissue, as well as development of gene cassettes for effective neural repair. The work will advance the field of bionics, an area where Australia is establishing international preeminence.Read moreRead less
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
Physiological, bahavioural and functional motor abilities in children with undifferentiated tongue movements during speech. A subgroup of children with speech disorders who have difficulty moving parts of their tongue independently during speech has been identified. This study aims to investigate if this is a unique phenomenon of the tongue during speech, or indicative of more generalized patterns of motor movement. This will enable us to explore the similarities between patterns of movement in ....Physiological, bahavioural and functional motor abilities in children with undifferentiated tongue movements during speech. A subgroup of children with speech disorders who have difficulty moving parts of their tongue independently during speech has been identified. This study aims to investigate if this is a unique phenomenon of the tongue during speech, or indicative of more generalized patterns of motor movement. This will enable us to explore the similarities between patterns of movement in the articulators during speech and non-speech tasks and the upper limb. In turn, this will inform the debate about motor control mechanisms for speech and other body movements, which would lead to more effective treatment regimes.Read moreRead less
Determinants of successful community transition for individuals with acquired brain injury and their families. Transition home following acquired brain injury (ABI) is a critical phase in which individuals and families are vulnerable. Unsuccessful transitions are characterised by events such as financial crisis, family breakdown, loss of work, social isolation, and institutionalisation. ABI does not discriminate, but there is a higher rate in Indigenous, rural and remote communities and amongst ....Determinants of successful community transition for individuals with acquired brain injury and their families. Transition home following acquired brain injury (ABI) is a critical phase in which individuals and families are vulnerable. Unsuccessful transitions are characterised by events such as financial crisis, family breakdown, loss of work, social isolation, and institutionalisation. ABI does not discriminate, but there is a higher rate in Indigenous, rural and remote communities and amongst younger people. The societal impact of ABI includes loss of income and livelihood, health and welfare dependence, and long-term accommodation support. Research into the determinants of successful transition will alleviate the personal, social and economic burden of ABI and inform policy and program priorities for appropriate Australian Government bodies.Read moreRead less
Bilateral Cochlear Implants for Children: Does a Second Implant Improve Language, Psychosocial and Other Outcomes? Severe-profound congenital hearing loss engenders significant costs to society. In 2005, specialised education cost -- on average $25,000 per child, loss of productivity cost -- $6.7 billion, and social security benefits were paid to approximately 129,000 individuals who were unemployed due to hearing loss. If bilateral cochlear implantation results in improved language, social dev ....Bilateral Cochlear Implants for Children: Does a Second Implant Improve Language, Psychosocial and Other Outcomes? Severe-profound congenital hearing loss engenders significant costs to society. In 2005, specialised education cost -- on average $25,000 per child, loss of productivity cost -- $6.7 billion, and social security benefits were paid to approximately 129,000 individuals who were unemployed due to hearing loss. If bilateral cochlear implantation results in improved language, social development, and academic outcomes, the community benefits arising will be greatly improved quality of life for these individuals and significant savings to society. In partnership with Cochlear Ltd, this study will provide some of the first data worldwide comparing the effects of an additional implant on language, social and educational outcomes.Read moreRead less
An investigation of respiration in stuttering. Australia leads the world in stuttering research, and this project will maintain that profile. The research aims to establish if breathing has a causal role in stuttering. The new knowledge produced will support or weaken current theories of the cause of stuttering and will contribute to understanding the nature of the disorder. In particular, it will be applied to develop more effective and efficient treatments for chronic stuttering.