Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
A Trial Of A Multidisciplinary, Group Based Intervention To Meet The Needs Of Men With Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$524,285.00
Summary
This study will test an innovative approach to meeting the physical and psychosocial needs of men with early stage prostate cancer using a randomised controlled trial. This novel approach involves a combination of individual and group-based consultations which encourages peer-to-peer support, promotes self-care and enhances appropriate multidisciplinary referrals and communication. It provides a new model of care for patients with chronic diseases that can be translated into clinical practice.
Predictors And Correlates Of Health-related Quality Of Life And Morbidity In Overweight/obese Adolescents: Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$512,525.00
Summary
There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and ....There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and impacts of overweight and obesity. The Health of Young Victorians Study was originally assembled in 1997 when the children were in Grades Prep-3. In addition to information on putative risk and protective factors for overweight-obesity and direct measures of height and weight, it is unique in having collected data on health-related quality of life (HRQoL) since children were first recruited during the early primary school years. Eight years after the first wave, the children will be adolescents in Grades 8-11. This third wave will retain a focus on HRQoL. Innovations include study of potential emotional, behavioural and physical consequences of childhood obesity that may in turn affect the natural history of obesity. This large, population-based longitudinal study will redress neglected aspects of child and adolescent overweight-obesity specifically identified in 2003 by the NH and MRC. As well as establishing whether a range of common problems are related to overweight-obesity, it will be able to shed light on mechanisms of adverse outcomes associated with adolescent overweight-obesity, and study protective factors predicting remitting overweight from childhood to adolescence that may inform preventive activities. The study will make an international contribution to knowledge about pathways, prevalence and preventive opportunities for child and adolescent overweight-obesity.Read moreRead less
Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Elucidating The Mechanism Of Action Of Dendrimer Nanoparticles Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Dendrimers are nanoparticles with highly branched structures and they are being developed as topical microbicides to prevent the sexual transmission of HIV. This study will determine how dendrimers block HIV entry into host cells so that we can design more effective inhibitors and microbicides.
The Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.