Deciphering Mechanisms Of Liver Allograft Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$520,964.00
Summary
The liver has paradoxical properties: it is the site of effective immune responses to pathogens, but under some circumstances, it is known to induce harmless immune responses. Liver transplants are more readily accepted than other organ grafts in the absence of immunosuppressive drugs but little is known about the mechanisms that prevent an effective response. This proposal aims to unravel these mechanisms. This project will have important implications for transplantation studies.
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.
The Biology Of Events Following Reactivation Of Herpes Simplex Virus.
Funder
National Health and Medical Research Council
Funding Amount
$388,522.00
Summary
Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the s ....Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the subject of much debate and have never been properly studied in the nerve cells in which the virus lives. Furthermore the way in which herpes simplex virus enters the processes of nerve cells and moves to the cell body will be studied by similar techniques. Such studies may contribute to the development of herpes simplex virus as a vector for gene therapy for treatment of diseases of the nervous system. The second part of the grant will examine the immune processes that occur in the skin during the early stages of a recurrent herpes simplex lesion. In particular there is a linkage between nerves and the major cells in the skin which present viral antigen to defensive T-cells. This link may provide a route for direct access of herpes simplex virus to these cells. In previous work the viral protein targets in infected skin cells for killer T-cells which infiltrate the skin have been defined. In this grant we also aim to find the stretches of amino acids which are specifically targetted by these cells.Read moreRead less
Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
Infectious And Lifestyle Determinants Of Non-melanoma Skin Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$983,711.00
Summary
Basal and squamous cell skin cancers are the leading cancers in Australia, with about 2% of the population developing them each year. As well as sun exposure, a number of other factors have been thought to effect these cancers. This study will examine if factors such as smoking, alcohol consumption and infection with certain skin related human papillomaviruses also increase their risk. Even a small effect may make a big difference when it comes to preventing these common cancers.
Elucidation Of Immune Mechanisms Underlying HSV Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$573,993.00
Summary
HSV-1 and -2 causes genital herpes, cold sores, encephalitis, potential fatal neonatal herpes, keratitis and blindness as well as severe disease in transplant patients. HSV infection also enhances the acquisition of HIV by 2-3 fold. Investigating the mechanism of immune response to HSV infection or components of HSV will assist in understanding immune control of HSV, HSV vaccine development, and assist in reducing in HIV spread.
Role Of Brm In Skin Tumour Progression From Benign To Malignant
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that ....Australia has the highest incidence of skin cancer in the world. Skin cancer is 3 times as common as all other cancers combined and continues to increase in incidence, particularly in the aging population. Skin cancer is caused by exposure to the ultraviolet radiation found in sunlight. Ultraviolet radiation causes the appearance of solar keratosis, or sunspots, benign lesions that are not particularly dangerous to human health. Some of these develop into malignant squamous cell carcinomas that can spread to other tissues and are potentially fatal. Little is known about the biological mechanisms involved in solar keratosis development into squamous cell carcinomas. We have identified the gene brm as being involved in this process. It has not previously been recognised that this gene is important for skin cancer development and therefore our preliminary studies have identified a potential new target. We will study the role of this gene in ultraviolet radiation induced skin carcinogenesis, determine whether it is mutated by ultraviolet radiation in human skin cancer, and what role in plays in some key biological processes in skin cancer development. This study will expand our understanding of malignant conversion during human skin carcinogenesis, the most prevalent human cancer in Australia.Read moreRead less
Cell Type Specific Biologic Responses To HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The way in which HIV alters the internal environment of its target cells to facilitate its growth will be examined. These changes enhance its ability to gain a toehold in the human body after entering the genital tract and its persistence for life in the brain and elsewhere in the body.
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less