Identification And Characterisation Of Nessy; A Novel Gene Important For T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identif ....This project aims to identify, and understand the function of, a new gene involved in the immune system. The Nessy mouse strain was developed in Prof. Goodnow s Medical Genome Centre at the Australian National University. It has a mutation in an unknown gene which causes a defect in T lymphocytes- white blood cells which are important for fighting infection. This project has three major aims: 1) to identify the gene. 2) to understand the defects in T lymphocytes caused by the gene. 3) to identify which other genes interact with the mutant gene. Thus will allow us to understand how the mutant gene causes the T lymphocyte defects. This project will improve our understanding of the development and functioning of T lymphocytes, which play a central role in the immune system. Since the genomes of mice and humans are very similar, it is likely that we will be able to identify a human counterpart to the Nessy gene.Read moreRead less
Fainting (syncope) is a common disorder leading to blackouts, which can cause injury. Breath-holding is a related problem in younger children also resulting in blackouts. Both of these conditions can run in families but little is known about what causes these events. We will study large families to identify the genes underlying these common phenomena. This will deepen our understanding of patterns of inheritance, improve genetic counseling, and lead to better diagnostic and treatment options.
Optimisation Of Salmonella Genotyping And Epidemiological Data Analysis For Detection And Investigation Of Outbreaks
Funder
National Health and Medical Research Council
Funding Amount
$508,051.00
Summary
Bacteria known as salmonella are the most important causes of food-borne diarrhoeal disease. They occasionally cause potentially fatal septicaemia, especially in young children and people with underlying disease. We estimate that more than 80,000 cases of salmonella infection occur in Australia, each year, at a cost to the community of $37 million. Salmonella are divided into more than 2000 different types, but one - called Typhimurium - causes about 40% of infections and a few others cause most ....Bacteria known as salmonella are the most important causes of food-borne diarrhoeal disease. They occasionally cause potentially fatal septicaemia, especially in young children and people with underlying disease. We estimate that more than 80,000 cases of salmonella infection occur in Australia, each year, at a cost to the community of $37 million. Salmonella are divided into more than 2000 different types, but one - called Typhimurium - causes about 40% of infections and a few others cause most of the rest. This means that is difficult to distinguish cases of salmonella infection that have originated from one source (an outbreak) from cases that have originated from another. Without this information, is it hard to track the source, which is usually inadequately cooked meat or chicken another food that has been contaminated with salmonella after preparation. There are several existing methods for fingerprinting salmonella, but they are quite slow or do not distinguish different strains well enough to identify outbreaks quickly. This means that sources of contaminated food are often not identified in time to prevent more cases occurring. We aim to develop a faster and more discriminatory system for fingerprinting salmonella, based on novel technology that can identify many small genetic sequences that occur in different combinations in different strains. As well, we will develop electronic scanning tools that will link the fingerprints of the salmonella strains with information about the people infected with them, such as the types of food and places where they have eaten, to identify patterns or clusters that indicate a common source. The more rapidly this can be done the sooner the source of contaminated food can be found and eliminated and additional cases can be prevented. This has important implications for public health - it will increase food safety and reduce illness and economic loss.Read moreRead less
Phylogeny As A Basis For Molecular Identification Of Pathogenic Fungi
Funder
National Health and Medical Research Council
Funding Amount
$440,750.00
Summary
Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ....Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ID of less common fungi. To improve clinical outcomes by prompt selection-initiation of the best antifungal regimes, and to truncate the interval from initiation of therapy to cure, early, accurate identification of the causative agent is crucial, making a fast identification to the species level after culture or direct from clinical specimens a necessity. A correct fungal identification can only be achieved if the phylogenetic relationships between the pathogenic organisms and their taxonomy is resolved. Gene detection is more reproducible than detection of morphological and biochemical differences. The proposal focuses on the establishment of an accurate phylogenetic system of pathogenic fungi, which will form the basis of a universally applicable molecular identification system and to develop a molecular reference database for human pathogenic fungi. This project will contribute sequence data of pathogenic fungi to the Tree of Life project. This project unites expertise in classical mycology, molecular biology, bioinformatics and infectious diseases, to develop an accurate phylogeny of medically important fungi, providing a unique opportunity to establish a quality controlled reference database accessible via the world-wide-web. This will provide a faster and more accurate ID of pathogenic fungi, which will lead to better clinical treatment.Read moreRead less
Crohn's disease is a severe, chronic inflammatory disease of the gut which affects up to 50,000 Australians. The majority of patients develop the disease in their twenties, with significant impact on their quality of life. Our preliminary work has identified a novel gene, which could potentially cause a critical reduction in the production of anti-bacterial proteins by cells in the small bowel. Exploring the function of this gene in relation to clinical outcome could lead to better treatment.
DETECTION OF OCCULT DISSEMINATED TUMOUR CELLS AND TUMOUR DNA IN EARLY STAGE OPERABLE BREAST CANCER PATIENTS
Funder
National Health and Medical Research Council
Funding Amount
$561,000.00
Summary
Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant ....Most of the reduction in breast cancer death rate in recent years is due to earlier diagnosis because of mammographic screening. Even among women with very favorable tumours, at least 20% will die of breast cancer. The risk increases to over 50% in less favorable cases of operable early breast cancer. Current practice relies very heavily upon prognostic factors such as lymph node status and tumour size in determining the risk of subsequent failure and the need for therapy. There is a significant risk of under treating good prognosis disease patients (20%) and over treating women with intermediate and high risk disease (40%). The first aim of the study is to use novel molecular methodologies to detect breast cancer cells in the blood of patients with early stage breast cancer at diagnosis. The presence of tumour cells will be correlated with the usual prognostic factors used in the management of women with breast cancer. The patients will be followed long-term to clarify the relationship between disseminated tumour cells in the blood and bone marrow and eventual outcome to assess the effectiveness of these new methodologies in patient management. We will also assess new molecular methodologies which will allow us to track very low levels of disease, and thereby monitor the effectiveness of treatment, and allow prediction of impending relapse. Studying the blood of breast cancer patients represents a unique opportunity for determining whether the cancer has spread before surgery and for monitoring of disease after surgical removal of the tumour. This study may prove invaluable in predicting disease free and survival outcomes and provide a more rational approach to the use of chemotherapy in patients with early breast cancer.Read moreRead less