A Congenic Approach To Analysing The Genomic Control Of Innate Immunity In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$240,156.00
Summary
In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry differ ....In addition to the lymphocytes, which are specialised white cells that can learn to defeat the infections that the body has been previously exposed, the body has a number of other defences. These non-learning systems have been honed by evolution and usually form an effective first-line of defence. This proposal deals with three: complement, and two highly specialised types of white blood cell, the Natural Killer cells and the NKT cells. The project will study mice especially bred to carry different versions of the genes which control these defences. Particular attention will be paid to their involvement in the autoimmune diseases, type 1 diabetes and lupus.Read moreRead less
Functional Genomic Analysis Of NK And NKT Cell Immune Control Of Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reas ....The major populations of white blood cells responsible for learned immunity to are the B cells, which make antibody against microorganisms like bacteria, and the T cells, which kill virally infected cells and help B cells produce antibody. The T and B cells occasionally attack the body s own tissues, resulting in autoimmune disease. These diseases include type 1 diabetes, lupus, and anaemia, and collectively represent the third commonest cause of morbidity and mortality in humans. The major reason why autoimmunity occurs is thought to be due to a failure in the mechanisms responsible for controlling such unwanted responses. Two other populations of white blood cells are involved in this regulation, termed NK and NKT cells, each of which release important cell hormones. The current project is designed to test whether defects in NK and NKT cells lead to autoimmune disease. For this purpose a special strain of mice (NOD mice) will be used. The reasons for their selection are: 1) they are highly susceptible to a range of autoimmune diseases including diabetes, lupus and anaemia, and 2) we and others have found that they are deficient in both NK and NKT cells. The proposed experiments are divided into two groups, one designed to characterise the nature of the defects in these cells and the other to identify the genes responsible for them. In this way it should be possible to shed light on the genetic basis of autoimmune diseases in general. The approach to be used involves sophisticated techniques of genetic analysis, which require production of special congenic lines of mice. These mice are like NOD mice but carry in addition to NOD genes genetic regions from a non-autoimmune strain with the potential to correct the defects in NK and NKT cells. In this way, it should be possible to pinpoint the disease susceptibility genes involved in causation of autoimmunity and to work out how they affect NK and NKT cells.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.
Anaemia In The Elderly: Epidemiology, Causes, Consequences And Optimal Transfusion Strategies
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Anaemia in the elderly (AE) is a common and increasing issue, which is often treated with blood transfusions. This project aims to investigate the causes and risk factors of patients who develop AE, and the impact of AE on health outcomes. The results will help define appropriate haemoglobin thresholds for AE, and provide information to develop appropriate guidelines for AE and transfusion management in the elderly.