Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less
Structural Characterisation Of Peptide Bound HLA-DQ2, HLA-DQ8, And Their Specific T Cell Receptors In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Celiac disease is an inflammatory condition resulting from an inappropriate immune response to dietary gluten, present in cereals such as wheat, rye and barley. In affected individuals, ingestion of gluten can result in bloating, chronic diarrhoea, and malabsorption. At present, the only treatment is strict adherence to a gluten free diet. This project will investigate the immune response to gluten on a molecular level, aiding in the development of new treatments(e.g. non-toxic wheat varieties).
Does Coeliac Disease Cause Ataxia Or Cognitive Impairment?
Funder
National Health and Medical Research Council
Funding Amount
$606,013.00
Summary
Coeliac disease (CD) is due to an allergy to a protein (gluten) found in wheat, barley and rye. It classically causes disease of the small bowel, resulting in impaired absorption of important nutrients, and is treated by a restrictive diet eliminating foods containing extracts of these grains. However, it has recently been found that CD is much commoner than previously thought (about 1 in 100-200), and often causes only non-specific symptoms. Two important conditions linked to CD by some, but no ....Coeliac disease (CD) is due to an allergy to a protein (gluten) found in wheat, barley and rye. It classically causes disease of the small bowel, resulting in impaired absorption of important nutrients, and is treated by a restrictive diet eliminating foods containing extracts of these grains. However, it has recently been found that CD is much commoner than previously thought (about 1 in 100-200), and often causes only non-specific symptoms. Two important conditions linked to CD by some, but not all, researchers are ataxia (incoordination) and impairment of thinking and memory. The problem is that many normal people (12% of the population) have antibodies to gluten, so that studies suggesting that sensitivity to gluten, as determined by the presence of antibodies, causes these brain disorders are not conclusive. That is, this could be a chance association. Furthermore, there is some evidence that damage to the coordination part of the brain (the cerebellum) from other causes may also cause antibodies to gluten. It is quite possible that antibodies to the cerebellum can cross-react with gluten, and vice versa. In this case, treating patients with ataxia and antibodies to gluten with the restrictive diet may be treating the result rather than the cause of the disorder. This project will study patients with CD (proven on small bowel biopsy) with sensitive, objective methods, including MRI, electronic measures of coordination, and psychological tests of thinking and memory, to see whether CD really is associated with these two problems. It will also study coordination and brain structure in a mouse model of CD. If the associations are proven, all patients with these disorders will need to be tested for CD, and treated with the restrictive diet if found to be positive. If not, clinicians will be confident that testing for anti-gluten antibodies would be irrelevant and misleading in these two situations.Read moreRead less
Proteins form up to 25% of our diet. The first step in protein absorption is the digestion of protein into smaller units called peptides and amino acids. Both components are subsequently taken up by specialised cells in the wall of the intestine. In this project we plan to study how protein absorption occurs at the surface of these intestinal cells and investigate why this process fails in malabsorption syndromes, where the uptake of amino acids is impaired.
How The Intestinal Microenvironment Controls Propulsion And Mixing Of Food In The Gut: Parallel Transduction Pathways
Funder
National Health and Medical Research Council
Funding Amount
$1,157,350.00
Summary
This project will identify the mechanisms that control the mixing of food with digestive juices, the absoprtion of nutrients from the gut to the blood stream and the excretion of waste. Disruption of these processes causes significant health problems and is associated with normal aging and many diseases. We will identify nutrients and other food components (eg spices) that switch gut from mixing to propulsion and hence identify targets to treat disorders of gut movement.
Neurodegeneration In The Ageing Brain: How The Pathways Leading To Aggregated Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$12,322,838.00
Summary
The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program ha ....The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program has identified several diagnostic and therapeutic avenues which are now being developed by the Pharmaceutical and Biotechnology industries. Much more research is still required for maximizing the chances of success using these approaches.Read moreRead less
The Prevalence And Trajectory Of Kidney Disease In Urban Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$94,515.00
Summary
The Study of Environment and Aboriginal Resilience on Child Health is a major NHMRC funded project looking at the health and illness of urban Aboriginal children in Australia. By working together with Aboriginal Community Controlled Health Services across urban and large regional centres in NSW the study team hope to better understand the causes of common diseases such as kidney and heart disease, and whether these first begin in childhood.
Computational Modelling To Understand Early-stage Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Rather than attempting to reverse neurodegeneration, therapeutic strategies must target the earliest possible stages of disease, when treatments have the potential to prevent or slow down pathological progression. The proposed project will employ computational modelling using functional MRI to deliver highly efficient and sensitive markers of Familial Alzheimer’s disease and Huntington’s disease progression to inform when in the progression of disease clinical trials should take place.
The Causes, Treatment, And Prognosis Of Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$190,445.00
Summary
The thyroid gland controls body metabolism and is crucial to life. Disorders of the thyroid place a severe burden on the health system. Yet despite this, much is unknown about the causes, optimal treatments, and prognosis of thyroid disease. In this NHMRC Early Career Fellowship, Don aims to advance knowledge and improve treatments of these common conditions, focusing on thyroid cancer, Graves’ disease, and Hashimoto’s thyroiditis.