The development of vaccines and better treatments for HIV-AIDS and Hepatitis C are urgent global health priorities. This Program will undertake studies to better understand effective immunity against HIV and hepatitis C, allowing the rational design and testing of novel vaccines and treatments. The Program brings together a team of researchers with skills in basic virology and immunology with those providing expertise in translating findings in the laboratory into human clinical trials.
The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to tes ....The team has been at the forefront of research on type 1 diabetes for over a decade. This form of diabetes is a major chronic disease from childhood, as well as accounting for at least 10% of adult-onset diabetes. It occurs when the body�s immune system attacks and destroys the beta cells in the pancreas that make insulin, the hormone that controls the level of glucose in the blood. The team was one of the first in the world, and is the only one in Australia, to develop screening programs to test and identify people at risk for type 1 diabetes. They showed that the underlying disease could start years before symptoms occurred and discovered genes that determine the rate at which the underlying disease progresses. They have also found evidence that the disease may be triggered by gut viruses called rotaviruses in genetically-susceptible individuals. They showed that type 1 diabetes could be prevented in a mouse model by getting the immune system to make a protective response to insulin, and then went on to apply this in at-risk humans in a controlled trial of intranasal insulin, the first of its kind. They have used genetic techniques not only to pinpoint the mechanisms responsible for killing the beta cells but also to modify the beta cells to make them resistant to attack by these mechanisms. The multidisciplinary approach of the team will be directed to further understanding the genetic and environmental factors underlying type 1 diabetes and the immune mechanisms, particularly involving special white blood cells called T cells, that kill beta cells. A molecular target of the immune attack, the parent of insulin called proinsulin, will be used, paradoxically, as a tool to regulate the immune system and avert the attack. This will be achieved by giving proinsulin via the mucosa of the naso-respiratory tract or via the bone marrow-derived stem cells, initiallyin the mouse model as a test of feasibility for human application. In parallel with these approaches to prevention, specially constructed viruses will be used to transfer several new genes into beta cells to improve their resistance to immune attack, so that they can be transplanted into people with established diabetes without the need for potentially toxic drugs that suppress the immune system overall. The integrated research of the team is helping to provide a sound, rational base for the eventual prevention and cure of type 1 diabetes.Read moreRead less
Understanding G Protein-Coupled Receptors (GPCRs): Accelerating Discovery From Concept To Clinic.
Funder
National Health and Medical Research Council
Funding Amount
$6,871,789.00
Summary
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors (and thus drug targets) in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Our Program addresses this knowledge gap, using GPCR models that are relevant to treatment of metabolic, cardiovascular and central nervous system disease.
Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Th ....Type 1 diabetes (T1D) is a major chronic disease affecting over 100,000 Australians. Its treatment and complications impose a significant burden on affected individuals and their families and on the health system. T1D occurs when the immune system attacks insulin-producing cells in the islet cells of the pancreas. The team has developed ways to identify at-risk people, defined immune and genetic causes of T1D and is undertaking prevention trials and Australia's first islet transplant program. Their multidisciplinary research is taking us closer to the prevention and cure of T1D.Read moreRead less
Structural Biology Of Cytokine Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$3,988,996.00
Summary
This Program will be focused on a group of protein hormones and their receptors, implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine the mechanism of receptor activation and in particular will seek to link different forms of receptor assembly to different functions. This information will help us develop new drugs with more specificity for certain hormone functions and thus less side-effects.
The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammator ....The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammatory or allergic disease, such as arthritis or asthma. This team of researchers from the Hanson Institute in Adelaide, combining expertise in molecular and cell biology, protein chemestry, structual biology and animal models, has been working together for over 10 years, investigating the molecular mechanisms involved in controlling the formation and activities of blood vessels and white blood cells. This program seeks to further that understanding, and to develop drugs that have the potential of ameliorating the inflammatory condition.Read moreRead less
Type 2 diabetes (T2D) is threatening the health of this nation and if unchecked will cripple our health care system. There are several problems: (1) The incidence of T2D is growing and we do not fully know why; (2) T2D involves defective insulin action but how insulin works normally is still unclear; (3) much research in this area is performed in laboratory cells or animals and the translation of this research to the human disease is yet to be fully realised; and (4) current therapies and diagno ....Type 2 diabetes (T2D) is threatening the health of this nation and if unchecked will cripple our health care system. There are several problems: (1) The incidence of T2D is growing and we do not fully know why; (2) T2D involves defective insulin action but how insulin works normally is still unclear; (3) much research in this area is performed in laboratory cells or animals and the translation of this research to the human disease is yet to be fully realised; and (4) current therapies and diagnostic markers for early disease prediction are inadequate. Our goal is to make progress in each of these areas.Read moreRead less
Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Colon Cancer: Receptors, Signalling And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$7,115,542.00
Summary
This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell gr ....This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell growth, survival and movement. Newly developed instruments and techniques will allow us to identify and detect the critical steps during the development of colorectal cancer and to design potent drugs to fight the disease. We have experience in conducting novel clinical trials in colon cancer and have developed imaging techniques for monitoring the effectiveness and safety of new anti-cancer drugs. Our collective scientific experience and ability to work in the clinic provides a unique opportunity for developing more effective treatments for colorectal cancer patients.Read moreRead less
Interactions Between Adaptable Pathogens, Drugs And The Human Host
Funder
National Health and Medical Research Council
Funding Amount
$5,727,327.00
Summary
The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellen ....The Centre for Clinical Immunology and Biomedical Statistics (CCIBS) represents a collaboration between Royal Perth Hospital and Murdoch University that has brought together internationally recognised expertise in clinical immunology, experimental biology and innovation in biostatistics and computing. These resources have been applied to a broad range of research issues within the broad framework of HIV and hepatitis C disease and treatment. CCIBS has become a leading centre of research excellence internationally, establishing a reputation for innovative approaches to host-viral interactions that are built on a long tradition of research into the population genetics of both human and viral genomes, combined with a willingness to negotiate complex computation and statistical challenges in order to faithfully reflect dynamic biological processes at a population level. An early recognition that large and integrated repositories of genetic and clinical data are fundamental to the research success in the genomic era has also led to the creation of the single most comprehensive repository of HIV genetic sequencing data in the world. The contributions that CCIBS has made to several distinct areas of research, including understanding viral adaptation to host immune responses, the development of genetic testing to predict drug hypersensitivity reactions, and causes of antiretroviral drug-associated toxicities, have been published in prestigious journals including Science, Nature, Nature Immunology, The Lancet, Proceedings of National Academy of Sciences, and The American Journal of Human Genetics, and have also resulted in numerous international collaborations that recognise the unique attributes that CCIBS has been able to bring to the global research effort aimed at understanding fundamental aspects of HIV and hepatitis C biology and treatment.Read moreRead less