Human Arylamine N-acetyltransferase Regulation And Function - Effect Of Genetic Poymorphisms.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase ....How we handle chemicals that enter our bodies depends on a series of enzymes that are responsible for breaking down the chemicals and eliminating them. The activity of many of these enzymes varies between individuals so our responses to chemicals and drugs is different for each individual. Some of the enzymes vary because of inherited mutations, but others vary because of the diets we eat and the environment in which we live. This project will investigate a major enzyme called acetlytransferase that has been implicated as a risk factor in diseases such as cancer, asthma, liver cirrhossis and adverse drug reactions. We plan to look at the enzyme in cells and determine what environmental factors contribute to its variation between individuals, and how this impacts on the genetic mutations that have been found in its gene. From these studies, we will have a much better undersanding of how different people metabolise foreign chemicals, and should be able to predict those most at risk of certain diseases.Read moreRead less
The Role Of Collagenase (MMP-1) In The Pathogenesis Of Human Pterygia
Funder
National Health and Medical Research Council
Funding Amount
$246,100.00
Summary
Pterygia are a common, recurrent, disfiguring, and sight-threatening disease of the human eye. This disease is extremely common world wide and particularly in the Australian aboriginal population. The triggers for this disease are unknown. Prolonged exposure to environmental elements, such as ultra violet (UV) light, is proposed to be the main initiating factor. Our previous studies have shown the important role played by a family of proteolytic enzymes (metalloproteinases) in the progressive an ....Pterygia are a common, recurrent, disfiguring, and sight-threatening disease of the human eye. This disease is extremely common world wide and particularly in the Australian aboriginal population. The triggers for this disease are unknown. Prolonged exposure to environmental elements, such as ultra violet (UV) light, is proposed to be the main initiating factor. Our previous studies have shown the important role played by a family of proteolytic enzymes (metalloproteinases) in the progressive and invasive nature of pterygia. We have significant preliminary evidence that a large percentage of patients with pterygia carry a mutation in one of these enzymes (collagenase-1). This is the most abundant enzyme expressed in pterygium tissue and probably plays a major role in invasion and progression in this disease. UV light activates cells in pterygia to induce expression of collagenase-1. This study will determine whether or not people with a genetic predisposition are more likely to develop pterygia and whether or not environmental factors, such as UV light, trigger progression of disease. If this is the case, then subjects with this genetic predisposition would be at increased risk for the development of pterygia (and their complications) and could be advised to take preventative measures to minimize the risk of developing this disease.Read moreRead less
Exploring The Function Of Breast Cancer-Associated Variants In Long Non-Coding RNAs
Funder
National Health and Medical Research Council
Funding Amount
$501,585.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known protein coding genes, suggesting that non-protein coding genes could be responsible for the associated risk. The aim of this proposal is to identify and characterise these non-coding genes. Understanding how sequences variations in these novel genes contribute to breast cancer will provide novel a ....Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known protein coding genes, suggesting that non-protein coding genes could be responsible for the associated risk. The aim of this proposal is to identify and characterise these non-coding genes. Understanding how sequences variations in these novel genes contribute to breast cancer will provide novel avenues for therapy.Read moreRead less
Genetic And Epigenetic Biomarkers In High Risk Colorectal Cancer: Predicting Risk Of Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
The main aim of this project is to define the prognostic and predictive significance of specific genetic events in patients with high risk (stage III) colorectal cancer. We attempt to explore the differences between primary tumours from patients with and without recurrence at three years. Data from the project will then be used to define a limited set of biomarkers which will aid in clinical decisions regarding the need for adjuvant chemotherapy after surgery for high risk colorectal cancer.
Inherited Genetic Variants As Prognostic Markers For Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$623,972.00
Summary
Bowel cancer is a major health burden. Surgical resection of the primary cancer is often possible at diagnosis, yet in many patients the cancer will recur. Together with mutations, inherited genetic variants influence the rate of bowel cancer growth. This study aims to identify inherited variants predictive of cancer recurrence. Improved prediction of recurrence will permit more targeted use of clinical interventions, tailored to the individual patient, ultimately improving patient survival.
Preventing The Evolution Of Transmissible Nitroimidazole Resistance In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$664,463.00
Summary
Tuberculosis kills more people than any other infectious disease. Unfortunately, the drugs available to us to treat TB are losing their efficacy due to the evolution of drug resistance. A new class of drugs, nitroimidazoles, has been developed, but there is a risk that the bacterium that causes TB will develop resistance to these compounds too. We will identify resistance mutations before they occur in the wild, to help identify them and find new compounds for which resistance cannot develop.
DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
Translation Of Glaucoma Blindness Genes To Improve Clinical Practice
Funder
National Health and Medical Research Council
Funding Amount
$856,795.00
Summary
Glaucoma is a common cause of irreversible blindness. It is currently difficult to predict which patients with the earliest signs of glaucoma will develop blinding stages of the disease. This study will investigate how genes and eye measurements can be used to predict the risk of developing severe glaucoma in people with early signs of disease. This will ensure that high risk individuals can access treatment early, while those at low risk can be spared unnecessary treatment and seen less often.