Epigenomic Marks As Indicators Of The Kinetics Of Gene Activation In Immune Cells.
Funder
National Health and Medical Research Council
Funding Amount
$619,805.00
Summary
Switching on an immune response involves major changes in the gene expression program of the immune cells. These changes in gene expression take place in the context of DNA packaged into the nucleus in a structure known as chromatin. We will investigate the relationship between chromatin and gene expression changes and how this relationship plays a role in the timing of the immune response. This information will be useful in developing novel means of controlling aberrant immune responses.
The Distinctive Roles Of Tissue Transglutaminase Isoforms In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$311,567.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Neuroblastoma caused by N-Myc oncogene accounts for about one third of the disease and represents a more aggressive subtype with a worse clinical outcome. This project aims to identify factors responsible for N-Myc-induced neuroblastoma initiation and factors sensitizing neuroblastoma cells to anti-cancer drugs, and to provide the basis for clinical trials of a combination therapy in children with neuroblastoma.
Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.
Targeting Histone Deacetylases For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,513.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Pancreatic cancer is the fourth leading cause of cancer death in adults. In this application, we will define how proteins called histone deacetylases promote cancer initiation and progression, and whether combination therapy with an inhibitor of the histone deacetylases and another anti-cancer agent exert efficient synergistic anti-cancer effects in animal models of neuroblastoma and pancreatic cancer.
Impact Of The Extension Of The Sydney Light Rail System On The Prevalence Of Physical Activity Participation
Funder
National Health and Medical Research Council
Funding Amount
$105,647.00
Summary
Regular participation in physical activity is associated with a range of physical and mental health benefits in adults, including reduced risk for cardiovascular disease, non-insulin dependent diabetes, overweight, hypertension, osteoporosis, some cancers and anxiety and depression. Regular participation in physical activity also improves the ability to meet the demands of work and to engage in leisure activities. Approximately half of all adult Australians are insufficiently active to gain the ....Regular participation in physical activity is associated with a range of physical and mental health benefits in adults, including reduced risk for cardiovascular disease, non-insulin dependent diabetes, overweight, hypertension, osteoporosis, some cancers and anxiety and depression. Regular participation in physical activity also improves the ability to meet the demands of work and to engage in leisure activities. Approximately half of all adult Australians are insufficiently active to gain the many health benefits associated with participation in regular physical activity. Modification of the physical environment is one avenue through which the prevalence of physcial activity participation might be increased. More specifically, there has been considerable speculation about the role of public transportation systems in increasing the proportion of adults who are adequately physically active, but no empirical evidence is available. This study will employ a quasi-experimental design to determine if the extension of the Sydney Light Rail System to Lilyfield results in an increase in the prevalence of physical activity (primarily walking) in the affected area, in comparison with a demographically similar area which is not affected by the light rail extension.Read moreRead less
Understanding The Role Of Human Lens UV Filters In Age-Related Cataract
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). ....Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). We believe, on the basis of our previous research, that human lens UV filter compounds play a major role in the protein modification that is the hallmark of age-related cataract and indeed may be the key factor in precipitating cataract. This proposal seeks to confirm this hypothesis. If this theory is confirmed, it opens the door to pharmacological intervention for cataract by, for example, treating patients (or possibly all people in middle age) with drugs that inhibit the synthesis of the UV filter compounds.Read moreRead less
The Interferon Inducible Transcription Factor IFI 16.
Funder
National Health and Medical Research Council
Funding Amount
$151,208.00
Summary
Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein pro ....Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein products of these genes in turn directly or indirectly mediate the necessary biological response to maintain cellular homeostasis. While there are hundreds of cellular genes that are induced following IFN stimulation, the molecular and biological functions of the protein products of many of these genes are often not known. IFI 16 is one such IFN-induced gene that belongs to a family of related genes found in human and mouse. Little is known about what role IFI 16 may play in an IFN response and how it may function to mediate its effect. The proposed study is aimed at understanding how IFI 16 is upregulated following treatment of cells with IFN, identifying which cellular genes may be directly regulated by IFI 16 and how this happens, and whether IFI 16 plays a role in the development of specific blood cells.Read moreRead less
Role Of Immediate Early Gene Induction And AP-1 Activation In HDAC Inhibitor Induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with ....Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with other existing therapeutics.Read moreRead less
Remodelling Of Bacterial Outer Membranes: Implications For Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
We have identified proteins located in bacteria that are responsible for growth and the transport of essential nutrients. We will use a combination of bacterial genetics, protein biochemistry and immunological techniques to fully characterize these proteins. This strategic knowledge has direct implications for vaccine development and National security, since similar species of bacteria were amongst the first biological weapons.