CD4 T Cell-mediated Tolerance And Autoimmunity To The Gastric H/K ATPase In Genetically Manipulated Mice
Funder
National Health and Medical Research Council
Funding Amount
$295,780.00
Summary
The immune system is designed to protect us from foreign pathogens such as bacteria and viruses. However, the system is not prefect and sometimes attacks an individual's own tissue (termed autoimmunity). Autoimmunity is not uncommon in the population, including diseases such as diabetes, rheumatoid arthritis and pernicious anaemia, to name a few. To study the details associated with why and how the immune system can turn on the host, we use animal models which mimic the human diseases. The model ....The immune system is designed to protect us from foreign pathogens such as bacteria and viruses. However, the system is not prefect and sometimes attacks an individual's own tissue (termed autoimmunity). Autoimmunity is not uncommon in the population, including diseases such as diabetes, rheumatoid arthritis and pernicious anaemia, to name a few. To study the details associated with why and how the immune system can turn on the host, we use animal models which mimic the human diseases. The model we use is a mouse model for autoimmune gastritis which is an organ-specific autoimmune disorder of the stomach. People with autoimmune gastritis produce a specific autoimmune response directed at the acid secreting cells of the stomach call parietal cells. Parietal cells also produced a substance called intrinsic factor which is needed for the absorption of vitamin B12 from the diet. The lack of vitamin B12 uptake results in abnormal red blood cell formation and anaemia; hence the term pernicious anaemia. One of the unanswered questions associated with the immune system is what regulates the whole system so that it does not induce autoimmunity in everyone. The mechanisms which control or prevent autoimmunity is the subject of much debate. There is good evidence that regulation of the immune system is performed by specific suppression by regulatory cells. Many important question about these cells remain unanswered. For example, it is not known how these cells are generated or how they prevent the autoreactive cells from performing their harmful behaviour. Using our animal model for autoimmune gastritis, we are addressing some of the questions which surround the events which induce and protect us from autoimmunity. By using mice in which most of the lymphocytes in the circulation are of the same specificity (TCR-transgenic), we can follow the fate of those cells and look for cells with different characteristics; such as the ability to supress an immune response.Read moreRead less
A Novel Mode Of Cytokine Receptor Assembly And Activation: Functional And Structural Characterization
Funder
National Health and Medical Research Council
Funding Amount
$621,322.00
Summary
This proposal will study 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
Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in signifi ....Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and eat away lung tissue. In addition, these substances enter the blood and muscle where they eat away muscle resulting in significant weight loss. Patients with COPD have severe difficulty in breathing because the lungs are damaged and do not function properly. This process, once started, cannot be reversed and there is currently no satisfactory therapy to help treat individuals with this terrible disease. People with COPD are prone to viral and bacterial infections of the lungs. These infections cause further inflammation, lung damage and difficulty in breathing. These infections place a tremendous burden on health care resources, have a huge effect on the quality of life and are a common cause of death. The reason why respiratory infections are so serious for people with COPD is unclear. Preliminary results from our laboratory show that a substance called GM-CSF, released from cells in the lung, may be involved in the development of COPD. Thus, the aim of this project is to use our mouse models of COPD to determine whether GM-CSF is involved in the development of COPD. The insights gained may lead to the identification of potentially novel ways to prevent and treat COPD.Read moreRead less
Determining The Structure Of A Soluble Cytokine Receptor Complex
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understandin ....There is a pressing need to develop improved therapeutics to treat many forms of cancer and respiratory diseases. This proposal concerns the biochemical investigation of a group of protein hormones and their associated receptors that are implicated in blood cell cancers and for which current treatments are only partly effective . Our work will focus on determining the 3-dimensional shape and function of this group of proteins in complex with one another which will provide us with an understanding of how these proteins communicate with one another. This information may provide a basis for the design of new drugs that can specifically block the activity of these protein hormones, thereby providing new treatment possibilities for these blood cell cancers.Read moreRead less