Autoimmune diseases are those caused by the body's immune system attacking the body's own tissues. One group of autoimmune diseases, termed the thyrogastric cluster appear to share genetic risk factors, because they tend to occur together - either in the same patient, or else in families. Some of the diseases within the thyrogastric cluster are known to be very complex genetically, while others appear to be much less complex. Furthermore, some animal models of autoimmune diease are genetically s ....Autoimmune diseases are those caused by the body's immune system attacking the body's own tissues. One group of autoimmune diseases, termed the thyrogastric cluster appear to share genetic risk factors, because they tend to occur together - either in the same patient, or else in families. Some of the diseases within the thyrogastric cluster are known to be very complex genetically, while others appear to be much less complex. Furthermore, some animal models of autoimmune diease are genetically simpler still. We have chosen to study the genetics of gastritis in mice that have had their thymuses removed on the third day of life, because this model has relatively few genes involved; we have found that only 4 genes affect the risk of disease. This means that it will give us the optimum chance of identfiying at least one of these genes. The methods used involve both selective breeding techniques and generating special gene transfer mice in which individuals from one strain will carry the inserted genes from another. In this way, we can identify exactly which genes affect the risk of disease. Once identified, the gene sequences will help us determine if the same gene plays a role in human disease, and if so, to develop new diagnostic tests and therapies.Read moreRead less
A Functional Genomic Approach To The Genetics Of Autoimmune (type A) Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$467,640.00
Summary
The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. T ....The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. This project studies a mouse model of autoimmune gastritis with the aim of identifying the genes that encode susceptibility to the disease in this model. Ultimately, this information should help us to devise therapies that can be applied to the clinical situation. We have previously identified the locations of the genes which are responsible for causing gastritis in these mice. Two of them are very close together on one chromosome and appear to be very important because they have the strongest effects. Furthermore, there is some evidence that these genes may also be involved in determining susceptibility to diabetes and lupus. This project aims to further characterise these genes by locating them more exactly and by examining their effect on mice not normally prone to gastritis.Read moreRead less
Molecular Diagnosis And Therapy Of Autoimmune Disease Using Translational And Reverse Translational Approaches
Funder
National Health and Medical Research Council
Funding Amount
$2,331,372.00
Summary
We plan to translate our recent discoveries on human gene variants and molecules produced by immune cells (follicular T cells) into effective therapies for autoimmune diseases. This will involve understanding the mechanisms by which the genes and molecules regulate immune tolerance, stratifying patients with autoimmune disease using newly identified biomarkers, trialling existing biologicals according to affected molecular pathway, and taking novel targets through to commercialisation.
Immune-associated Genetic Variation And Autoimmune Disease.
Funder
National Health and Medical Research Council
Funding Amount
$1,346,721.00
Summary
Understanding the genes that underpin the immune system is vital for studying the causes and effects of diseases. In particular, autoimmune diseases are strongly associated with an individual having certain genetic types. We plan to develop methods to type immune-related genes very cheaply so they can be studied in very large samples. We will apply the methods we develop to genetic studies of psoriasis and multiple sclerosis, and make data and methods available to other scientists.
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.