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
The pathogen Cryptococcus neoformans is responsible for hundreds of thousands of deaths annually. If the infection is survived, relapse caused by evolved forms of the original infecting strain is common. Our research has uncovered similar genetic changes in isolates from unrelated patients that implicate epigenetic processes in relapse and reveal potential vulnerabilities of the pathogen. The proposed work is to investigate these changes to assist in our antifungal drug development efforts.
Links Between Inflammatory Activity, Autoantibodies, And Cardiovascular Disease In Patients With SLE.
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
People with lupus are at increased risk of heart attack and stroke. For women aged 30-44 the risk is as much as fifty times higher than in women without lupus. Only some of this risk is due to well known factors like high blood pressure and cholesterol. We are looking at other possible causes of heart attack and stroke in people with lupus - with blood tests and heart scans. We hope this will identify who is at risk and what can be done to prevent them from suffering a heart attack or stroke.
Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
Finding Therapeutic Targets For An Opportunistic Human Fungal Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$404,068.00
Summary
Penicillium marneffei is a fungus that causes disease in patients with depressed immunity. This project models this infection in zebrafish, which have advantages for modelling infectious disease. It uses fluorescent fungi and fish with fluorescent immune cells to study the way white blood cells fight this infection, and mutant zebrafish and mutant fungi to find new therapeutic targets in the host-pathogen interaction.
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
There has been no significant breakthrough in the treatment of Systemic Lupus Erythematosus (SLE) for over 50 years. Treatment continues to rely on non-specific immunosuppressant drugs and glucocorticoids (GC, or ‘steroids’), and the impact on patients includes high mortality and poor quality of life. In this proposal, I will validate novel endpoints which will break the impasse in SLE drug development and develop tools for minimising GC use in SLE.