Molecular Epidemiology Of Antibiotic Resistant Salmonella Enterica Strains Causing Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$493,767.00
Summary
Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from ot ....Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from other sources. Salmonella strains harboured by food-producing animals are the source of most of the food contamination.Tracing the source of individual resistant strains is essential for eradication and as there are many Salmonella types, some of which are found associated only with specific animals or birds, accurate identification is needed. The proposed work will make this process more accurate by using molecular techniques to unequivocally establish suspected connections and reveal further ones that are difficult to discern using current data and methods. This should decrease the number of infections due to resistant strains.Read moreRead less
The Mechanism Of Action Of New 5-nitroimidazole Drugs Which Are Effective Against Metronidazole-resistant Giardia
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
We have discovered new 5-nitroimidazole drugs which can overcome giardial resistance to metronidazole, the most prescribed 5-nitroimidazole drug to treat giardiasis. We will focus on defining mechanisms of action of these new 5-nitroimidazole drugs in the anaerobic gut protozoan parasite Giardia. Using biochemical techniques, we will determine whether our potent new drugs are activated more efficiently by the same mechanisms as metronidazole or by novel enzyme pathways in the parasite.
Interactions Between The Malaria Parasite's Chloroquine Resistance Transporter And Antimalarial Drugs
Funder
National Health and Medical Research Council
Funding Amount
$485,641.00
Summary
The malaria parasite is a single-celled organism which invades the red blood cells of its host. The aim of this project is to characterize the parasite protein responsible for conferring resistance to chloroquine, and to study its interaction with other antimalarial drugs. The parasite's susceptibility to chloroquine, and other drugs, is altered by small changes in this protein. This work will advance our understanding of the increasingly widespread phenomenon of antimalarial drug resistance.
Molecular And Cellular Determinants Of Tubulin-targeted Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$484,500.00
Summary
Cancer is the leading cause of death in developed countries. Despite advances in the use of combination chemotherapy, drug resistance is the major cause of treatment failure. An important component in the treatment of many childhood and adult cancers are the antimicrotubule agents. These drugs target an important part of the cell skeleton called the tubulin-microtubule system that is responsible for many important events including cell division. It is the ability of these drugs to disrupt cell d ....Cancer is the leading cause of death in developed countries. Despite advances in the use of combination chemotherapy, drug resistance is the major cause of treatment failure. An important component in the treatment of many childhood and adult cancers are the antimicrotubule agents. These drugs target an important part of the cell skeleton called the tubulin-microtubule system that is responsible for many important events including cell division. It is the ability of these drugs to disrupt cell division in cancer cells that makes them so effective and such important targets for new drug design. Unfortunately, the reasons why tumours develop resistance to these drugs or even why some tumours do respond well is not understood. This proposal will determine how the makeup and stability of the tubulin-microtubule proteins influences how these drugs work in both childhood and adult tumour cells. Finally, components of drug resistant tumour cells will be examined using technology that allows us to simultaneously separate and identify hundreds of proteins some of which may provide useful targets for the design of new drugs for the treatment of cancer. To improve cancer survival rates it is essential to accurately target the use of existing drugs and to identify new targets for anticancer drug development.Read moreRead less
Metabolomic Analysis And Membrane Transport Proteins In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$368,875.00
Summary
The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the ....The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the things hampering us in our efforts to develop new antimalarial drugs is our relatively poor understanding of the sorts of biochemical pathways that the parasite relies on to support its high rate of growth and replication inside the red blood cell, as well the biochemical mechanisms that enable it to becomes drug-resistant. In this study we will use a range of modern analytical techniques to carry out the first detailed survey of the biochemical composition - the so-called metabolome - of the parasite. We will investigate how this changes in response to nutrient deprivation, in response to mutations in genes which play a key role in antimalarial drug resistance and in response to changes in the expression of genes encoding proteins which we believe to be involved in the uptake of nutrients by the parasite. This project will provide us with a wealth of new information about the biochemical make-up of the parasite, and it will provide new insights into the biochemical pathways that are operating and which might be targeted with new drugs. The work is likely to provide new insights into mechanisms of antimalarial drug resistance. It will also form the basis for a strategy that is likely to be extremely useful in helping us to ascribe function to the many genes involved in the biochemistry of this important human pathogen.Read moreRead less
Actions Of The Polyphenol Epigallocatechin 3-gallate On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$409,746.00
Summary
This project will determine whether the bioactive compound in green tea (called EGCG) can reduce insulin resistance by enhancing the ability of insulin to open very small blood vessels (called capillaries) in muscle. Opening more capillaries will help glucose to be stored in muscle, thus alleviating insulin resistance. Findings from these studies may have important impact on the management of insulin resistance and type 2 diabetes.
Obesity-related Inflammation And Insulin Resistance In Chronic Liver Disease: Exercise And Diet As Treatment Options
Funder
National Health and Medical Research Council
Funding Amount
$540,509.00
Summary
The two most common types of liver disease in Australia are chronic hepatitis C (Hep C) and fatty liver disease and both result in more severe liver injury when the person is overweight. We propose to test if weight loss through lifestyle changes such as improving diet or increasing exercise are suitable treatment alternatives for people living with liver disease. This will help doctors better advise patients as to what they can do themselves to improve the health of their liver.
Genetic Analysis Of Drug Resistance In Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Treatment for childhood leukaemia fails in approximately 25% of children owing to resistance to the drugs being used. Our recent evidence suggests that only a few rare leukaemic cells are initially resistant at the commencement of treatment. This project aims to isolate these rare cells and to look for genetic changes in them which might account for their resistance. Hopefully an understanding of the genetic basis for drug resistance will lead to better means of overcoming it.
Insulin As A Regulator Of Postprandial Lipaemia In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$226,097.00
Summary
People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in ou ....People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.Read moreRead less