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
Erythropoiesis Stimulating Agents are used to correct the anaemia associated with kidney disease, and cost Australia around $100m in 2004. The optimal target haemoglobin remains the subject of intense debate despite several large trials in the area. This project will use pooled data from these trials to provide a definitive analysis of the overall harms and benefits associated with different targets for the first time and will guide the use of these expensive drugs to maximise patient benefit.
So Like Your Mum! Is The Health Of Mothers In Far North Queensland Reflected In The Nutrition And Growth Of Their Children In Early Life?
Funder
National Health and Medical Research Council
Funding Amount
$96,631.00
Summary
The health, nutrition and growth of a baby reflect the health and nutrition status of its mother. We will link routine health service information for Indigenous mothers with information on the growth, haemoglobin and health of their young children to identify key factors in a mother’s pregnancy and before, influencing the future health and development of their babies. This study will shape interventions to improve the health of mothers, and thus improve the health of their children through life.
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
Myelodysplastic Syndrome And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$562,654.00
Summary
We are interested in how myelodysplastic syndrome (MDS) affects the function of the bone marrow. We believe that changes associated with anaemia of MDS cause the bone marrow to be altered. This proposal addresses this question and explores new treatment approaches
The Role Of Soluble Transferrin Receptor In The Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$539,607.00
Summary
Iron is both essential for health and toxic in excess so the body very tightly regulates how much iron is absorbed from the diet. One of the most important regulators of dietary iron absorption is the iron demands of developing red blood cells. In this project we will investigate how developing red blood cells signal changes in iron absorption. An understanding of this process will be of great benefit in the analysis and treatment of important blood diseases and disorders of iron metabolism.
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
IV Iron For Treatment Of Anaemia Before Cardiac Surgery (ITACS Trial)
Funder
National Health and Medical Research Council
Funding Amount
$2,285,290.00
Summary
Our aim is to evaluate intravenous iron to treat anaemia in 1000 patients waiting for their cardiac surgery. This could reduce the risks of the operation and enable patients to recover faster and can go home earlier.