The Design And Synthesis Of Sialyltransferase Inhibitors As Anti-metastatic Agents
Funder
National Health and Medical Research Council
Funding Amount
$273,629.00
Summary
The prevalence of cancer and, in particular, cancer that spreads throughout the body has risen over the past twenty years in the human population and causes significant human mortality. A correlation between some of a cancerous cell's surface componentary and the ability of this cell to spread throughout the body has been established. This research project will provide a range of chemical entities (probes) that will intervene in this spreading process (metastasis). These probes will be the basis ....The prevalence of cancer and, in particular, cancer that spreads throughout the body has risen over the past twenty years in the human population and causes significant human mortality. A correlation between some of a cancerous cell's surface componentary and the ability of this cell to spread throughout the body has been established. This research project will provide a range of chemical entities (probes) that will intervene in this spreading process (metastasis). These probes will be the basis for a drug discovery programme that targets a particular aspect of the spreading process. Through molecular modelling, drug candidate synthesis and evaluation of these compounds in relevant test tube (in vitro) assays it is envisaged that a number of candidate compounds will then be evaluated in an animal model (in vivo assay). The technology to be used in this project is comparable to that which we used in the discovery of the recently approved influenza drug, Relenza?.Read moreRead less
An Investigation Of Vibrio Cholerae Sialidase As A Target For Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The prevalence of the disease Cholera still causes significant human mortality, in particular in underdevloped countries. The process that enables the cholera toxin to cause signficant damage is now partly understood. This research project will provide a range of chemical entities (probes) that have the potential of intervening in this process . These probes will be the basis for a drug discovery programme that targets toxin binding. Through molecular modelling based on protein structural inform ....The prevalence of the disease Cholera still causes significant human mortality, in particular in underdevloped countries. The process that enables the cholera toxin to cause signficant damage is now partly understood. This research project will provide a range of chemical entities (probes) that have the potential of intervening in this process . These probes will be the basis for a drug discovery programme that targets toxin binding. Through molecular modelling based on protein structural information, drug candidate synthesis and evaluation of these compounds in relevant test tube (in vitro) assays it is envisaged that a number of candidate compounds will be then further optimised for eventual pre-clinical investigation. The technology to be used in this project is comparable to that we have used in the discovery of the recently approved influenza drug, Relenza .Read moreRead less
Functional Analysis Of The Ym2 Chitinase-like Lectin In Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response tha ....The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response that is biased toward production of allergy-related T helper 2 cytokines of which interleukin (IL)-13 is a potent mediator of disease. However, the molecular processes linking IL-13 with abnormal airway wall changes are unclear. To identify previously uncharacterised IL-13-related molecules, we used a protein profiling approach that identified a novel lectin (carbohydrate-binding protein) termed Ym2, which is secreted abundantly into the airway fluid of mice in which allergic airways disease has been induced. Preliminary studies suggest that Ym2 is an intermediary of IL-13 that is involved in respiratory dysfunction. This project aims to work out how Ym2 interacts with the molecules and cells of the respiratory tract to regulate allergic disease. Specific inhibitors of Ym2 will be developed to examine what happens to allergic responses when Ym2 can t function; transgenic mice will be developed to determine if we see features of allergy when Ym2 is over-expressed in the normal lung, and human samples will be screened to identify the human counterpart of Ym2 and whether this counterpart is secreted into the lung fluid of asthmatics. Defining the mechanism by which Ym2 regulates the pathogenesis of allergic disease will not only contribute to our basic understanding of the processes underlying asthma pathology, but also generate new information for better design of therapeutics directed against specific mediators of this debilitating and widespread disease.Read moreRead less
The Role Of Dietary FODMAPs In The Genesis Of Symptoms In Patients With Irritable Bowel Syndrome And Crohns Disease.
Funder
National Health and Medical Research Council
Funding Amount
$418,818.00
Summary
Irritable bowel syndrome occurs in one in seven Australian adults. Crohn's disease affects 0.2% of the population. Both conditions affect the young and productive members of our society and are characterised by lower abdominal pain, bloating, wind and altered bowel habit. Our team has identified dietary triggers that may be responsible for the induction of symptoms in the majority of patients. These triggers involve a group of carbohydrates (FODMAPs) that are found in a wide variety of food.
Glycan Specificity And Dependence In Rotavirus Host Cell Invasion
Funder
National Health and Medical Research Council
Funding Amount
$636,602.00
Summary
Rotavirus is a global pathogen that causes acute gastroenteritis resulting in dehydration and high levels of infant mortality. Annually, infections cause 138 million cases of infantile gastroenteritis and an estimated average of 600,000 deaths. Within Australia ~10,000 children under 5 yrs old are admitted to hospital annually with severe rotavirus-induced diarrhoea. This project will investigate the role of carbohydrates in rotavirus infection to help design new vaccines and inhibitors.
The Predictors Of Type 2 Diabetes In The Melbourne Collaborative Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$318,136.00
Summary
In 1990 we set up a long-term study of diet and health. The aim was to measure diet and other risk factors in healthy people in order to see how they might affect future development of type 2 diabetes (also known as adult onset or non-insulin-dependent diabetes). To do this we recruited 41,500 Melbournians aged 40 to 69 years, measured what they ate and drank, and collected information on other aspects of lifestyle, medical history, and family history of common diseases. All had height and weigh ....In 1990 we set up a long-term study of diet and health. The aim was to measure diet and other risk factors in healthy people in order to see how they might affect future development of type 2 diabetes (also known as adult onset or non-insulin-dependent diabetes). To do this we recruited 41,500 Melbournians aged 40 to 69 years, measured what they ate and drank, and collected information on other aspects of lifestyle, medical history, and family history of common diseases. All had height and weight and blood pressure measured and gave a blood sample. People were selected so that men and women, and migrants from Italy and Greece would be included. In this way we could widen the range of dietary habits and other lifestyle indicators. Since then participants have completed another questionnaire and occurrences of disease have been noted from self-reports and from examining medical records. We want to analyse data from the 700 people in the study who have developed type 2 diabetes. First we will analyse data collected on all 41,500 (on joining the study, and at follow up). Next we will use data from the 700 people with diabetes and 1400 of similar age and sex who have not developed diabetes. This study will focus on measuring substances in the blood. We want to measure a range of fats, vitamins, antioxidants, a marker of the health of blood vessels, as well as sex hormones and related substances. We will then be able to estimate what affect these factors have on the risk of getting diabetes. We will also be able to see if any of them act together to make the risk of diabetes much higher in certain men and women. This work should identify what changes in lifestyle, especially diet, could reduce the risk of diabetes, and help us understand why this is so. This is important because every year more and more people are developing diabetes.Read moreRead less