Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.Read moreRead less
Characterisation Of Cell-mediated Immune Responses In Burkholderia Pseudomallei Infection
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and ot ....The bacterium Burkholderia pseudomallei, causes a life threatening condition known as melioidosis. Melioidosis is emerging as an important infectious disease in tropical regions of Australia and South East Asia. Death rates following acute disease are extremely high. Despite the importance of B. pseudomallei in tropical public health, very little is known regarding how the body's defence mechanisms prevent the spread of infection. The wide distribution of melioidosis in tropical Australia and other parts of the world, and the lack of basic scientific information regarding this disease, has prompted this study. The bacterium lives within the body's cells and therefore does not respond well to standard antibiotic treatment. Although some of the basic immune mechanisms have been identified, how protection to the organism develops remains unclear. In this project we will investigate the effect of B. pseudomallei on immune cells or lymphocytes. This study will determine the patients' immune responses to the bacteria causing the disease. Our research team has already successfully carried out work on several different aspects of melioidosis. The characterisation of the basic immune function determined in the proposed study will provide the scientific basis for improvement in treatment and the development of possible preventive strategies against melioidosis.Read moreRead less
Immune Regulation, Cellular Trafficking And Chemokine Receptors In Intestinal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell ty ....The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell type, known as a regulatory T cell (T reg), is a powerful candidate cell as a master controller of intestinal inflammation. We know that T cells move to various sites in the body under the influence of hormone-like proteins known as chemokines, but the existence of T reg cells in the intestine, their characteristics, their behaviour and their specific response to chemokines, are all unknown. These studies aim to examine the presence and nature of T reg cells in human and mouse intestine, in both health and inflammation, and to explore how these cells migrate into the gut under the influence of chemokines. This knowledge will help in our understanding of intestinal immunity and endogenous regulation of immune responses, and will provide new targets for treatment of inflammatory bowel disease, and potentially other inflammatory diseases.Read moreRead less
Host Resistance And Protection Against Oral Candidasis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these ....Candida albicans is an important opportunistic pathogen, that is widely represented in general medical and dental practice, as well as in the hospital environment. Clinical observations indicate that defects in innate immunity predispose patients to disseminated infection, whereas a weakened cell-mediated immune response is commonly associated with chronic oral infections. Animal models of both chronic and acute oral candidiasis have been developed and characterised by the applicants, and these have clearly implicated T cells in the process of recovery from primary infection. The models will now be used to analyse the effector mechanisms that lead to clearance of the yeast from the oral cavity, with a particular focus on the role of phagocytic cells, and their interaction with T cells. The acute model will be used to identify immunological variables that can act as markers of protection, and the effectiveness of therapeutic manipulations will be evaluated in the chronic model, with the ultimate aim of developing a protective vaccine for human infections.Read moreRead less
Comparative Effectiveness Of Vaccine-induced SIV-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$607,797.00
Summary
A HIV vaccine remains elusive. Although killer T cell immunity can provide partial protection from HIV disease, we don't know the best type of killer T cells to induce by vaccination. This project compares multiple HIV vaccine strategies in macaques. We will carefully study the quality of killer T cell immunity induced using novel and cutting-edge assays. We will identify the requirements for effective killer T cell immunity to HIV.