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
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
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
This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology ....This program application seeks to draw on the skills of a world leading group of Australian researchers to bring novel HIV vaccine designs to clinical trials, improve vaccine design and create new opportunities for commercialisation. The Chief Investigators, Prof David Cooper, Prof Peter Doherty (Nobel Prize winner), A-Prof Stephen Kent and Prof Ian Ramshaw, have achieved major scientific developments including: innovative collaborative clinical trials, cutting edge research in T cell immunology, the establishment of the only PC3-level nonhuman primate facility in the Southern hemisphere, T cell immunogenicity of the DNA-viral vector prime-boost vaccine regimens and ground-breaking research on cytokine co-expressing viral vector vaccines. The Principle Investigators also have a record of substantial achievement in relation to HIV and T cell biology as well as novel vaccination technologies. There is a strong history of successful collaboration among this group leading to the award of major NIH funding.Read moreRead less
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
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.
Molecular Determinants Of Risk, Progression And Treatement Response In Melenoma
Funder
National Health and Medical Research Council
Funding Amount
$12,947,193.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life because it is the common cause of cancer death in younger adults. The investigators are all associated with the Melanoma Institute Australia, incorporating the Sydney Melanoma Unit (SMU). MIA is the world’s largest clinical service dedicated to the treatment of melanoma, treating >1500 new melanoma patients annually and mainta ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life because it is the common cause of cancer death in younger adults. The investigators are all associated with the Melanoma Institute Australia, incorporating the Sydney Melanoma Unit (SMU). MIA is the world’s largest clinical service dedicated to the treatment of melanoma, treating >1500 new melanoma patients annually and maintains a repository of clinical data on melanoma and a large melanoma tissue bank. The Program has also recruited large numbers of people from the community, as well as people with a strong family history of melanoma, in order to study its causes. It aims to utilise these internationally-recognised resources to develop a scientific basis for 1) improved management of individuals at high risk for development and progression of melanoma, and 2) improved treatment of patients with early and disseminated melanoma, in an era of rapid change in the prospects of successfully treating this dangerous cancer. The Program will do this by consolidating and extending its existing collaborative research, supported by NHMRC since 2006.Read moreRead less
MOLECULAR AND CELLULAR PATHOGENESIS OF HUMAN LIVER DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$4,928,323.00
Summary
n humans, chronic liver diseases cause cirrhosis of the liver in some but not all individuals. This leads to protracted ill-health, complications (fluid retention in the abdomen, confusion, bloodstream infections, kidney failure, liver cancer) resulting in hospitalisation, liver transplantation and premature death. In Australia, cirrhosis is an important cause of death and of years of potential life lost, while liver cancer has recently doubled and is predicted to treble by 2020. The common caus ....n humans, chronic liver diseases cause cirrhosis of the liver in some but not all individuals. This leads to protracted ill-health, complications (fluid retention in the abdomen, confusion, bloodstream infections, kidney failure, liver cancer) resulting in hospitalisation, liver transplantation and premature death. In Australia, cirrhosis is an important cause of death and of years of potential life lost, while liver cancer has recently doubled and is predicted to treble by 2020. The common causes are hepatitis C, fatty liver disorders, alcohol and hepatitis B; when 2 of these are present together, there is a higher risk of cirrhosis. This program aims to unravel the pathological processes which cause cirrhosis at the molecular and cellular levels, in order to understand why some people are at higher risk. These processes could result from genetic predisposition, other constitutional factors (age, gender) or from lifestyle factors (overnutrition, inactivity, alcohol). The 3 chief investigators from Westmead s Millennium Institute and the Centenary Institute of Royal Prince Alfred Hospital are international experts in hepatitis C, non-alcoholic steatohepatitis (NASH) and other fatty liver disorders, autoimmune hepatitis, liver transplantation, and scarring processes that lead to cirrhosis of the liver. The new knowledge that will result from these studies will be used to help prevent people developing severe forms of chronic liver disease, and for treating cirrhosis if it has already occurred.Read moreRead less
Pathogenesis, Treatment And Prevention Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$9,752,075.00
Summary
Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseas ....Bacterial infectious diseases remain a serious threat to human health, accounting for over 10 million deaths each year. This is a broad-based collaborative proposal, building on our previous achievements. Its aim is to better understand the dynamic interactions between major disease-causing bacteria and their human hosts, and to directly apply this new knowledge to the development of improved vaccines and novel treatment strategies. These are urgently needed to combat bacterial infectious diseases in the 21st centuryRead moreRead less