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
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100170
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Bioaffinity mass spectrometry infrastructure to identify small molecules binding to therapeutic targets. The development of anti-infective therapies is challenging because the underlying biology and biochemistry of pathogen virulence is not yet completely understood. This mass spectrometer facility will be used to identify small molecules suited for development into new therapies for malaria, tuberculosis and HIV.
Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). GPCRs are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
New methodology for the manufacture of opioid pharmaceuticals and the discovery of novel opiate receptor ligands. Semi-synthetic opiates are important analgesic agents and are used in the treatment of alcohol and opiate dependence. This project will focus on the application of new, greener and more efficient methods for the preparation of these medicinal agents.
Subtype selectivity and functional bias of receptor positive allosteric modulators for understanding models of pulmonary disease. G-protein-coupled receptors (GPCRs) are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
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