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.
Microarray-targeted Candidate Gene Approach To Finding Ovarian Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$612,933.00
Summary
We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them t ....We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them to be targeted for screening, and for intervention studies, as well as providing fundamental insight into the etiology of ovarian cancer.Read moreRead less
Identification Of Novel Low Penetrance Genes Associated With Melanoma Risk
Funder
National Health and Medical Research Council
Funding Amount
$399,830.00
Summary
Using pools of DNA samples we will conduct a genome-wide association study for melanoma predisposition genes. The most promising candidate genes will be followed up by sequencing and further geneotyping of additional SNPs in order to identify the causal variants.
Inosine-5' Monophosphate Dehydrogenase (IMPDH) is an enzyme responsible for providing a form of energy to cells, so that they may undertake their correct functions. Recently, we have demonstrated that IMPDH also has a role in the formation of fat droplets within cells, when they are exposed to excessive nutrients. In mammals, excess consumed energy is stored as fat droplets within all cells. In fat cells, the energy is stored in very large droplets, and we see this as extra body fat. This is som ....Inosine-5' Monophosphate Dehydrogenase (IMPDH) is an enzyme responsible for providing a form of energy to cells, so that they may undertake their correct functions. Recently, we have demonstrated that IMPDH also has a role in the formation of fat droplets within cells, when they are exposed to excessive nutrients. In mammals, excess consumed energy is stored as fat droplets within all cells. In fat cells, the energy is stored in very large droplets, and we see this as extra body fat. This is sometimes associated with an alteration in the hormone production of the cells, leading to problems such as diabetes. In other cells, the excess energy is stored as tiny fat droplets (lipid bodies) that can adversely affect the function of the cell. We have shown that blocking the action of IMPDH can interfere with the accumulation of fat in both fat cells and other types of cell. This suggests that IMPDH has an important role in the development of obesity and associated problems such as diabetes. In this study we aim to investigate in detail the role of IMPDH in the accumulation of fat droplets in cells. We will do this by looking at the effects of different forms of IMPDH in different cell types, including human fat cells. We will also study cells and animals with increased or decreased amounts of IMPDH, and investigate the effects of this on the development of increased fat stores and insulin resistance. These studies will increase our understanding of the role of IMPDH in the development of obesity, and may lead to identification of new avenues of treatment for obesity and type 2 diabetes.Read moreRead less
KILLING OF MYCOBACTERIUM TUBERCULOSIS IN MACROPHAGES VIA THE P2X7 RECEPTOR
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Tuberculosis remains an enormous global health problem. Some 32% of the world population are infected, with over 1 million persons dying each year. The risk of an infected individual developing clinical disease ranges from 2-23% for their lifetime. We know that both environmental factors, such as declining socio-economic conditions, and genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully accou ....Tuberculosis remains an enormous global health problem. Some 32% of the world population are infected, with over 1 million persons dying each year. The risk of an infected individual developing clinical disease ranges from 2-23% for their lifetime. We know that both environmental factors, such as declining socio-economic conditions, and genetic risk factors such as HLA type contribute to the likelihood of an individual developing disease, but current known factors are insufficient to fully account for the risk attributed to genetics. The aim of this project is to investigate another potential risk factor involved in the development of tuberculosis, that of P2X7 receptor function. A natural compound, ATP, when added to macrophages is able to kill tuberculosis organisms residing within the macrophage. This process occurs when ATP activates the P2X7 receptor. We have recently identified a mutation in the P2X7 receptor, which causes a loss of receptor function. Individuals who have this mutation are unable to respond to ATP and hence may be unable to kill tuberculosis. Our studies will determine if the mutation we have identified in the P2X7 receptor prevents or inhibits ATP mediated killing of mycobacteria. Furthermore we will determine the frequency of this mutation in TB patients and the general population to determine if this mutation in the P2X7 receptor is a risk factor for the development of tuberculosis disease.Read moreRead less
The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment o ....The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment of heart attack and stroke. The currently available drugs are not universally effective and their use is often limited by adverse reactions. In this submission, we propose to investigate the efficiency of a new drug that will prevent clot formation and will also tackle inflammation. This drug is a derivative of an enzyme that is already present on platelets and cells that line blood vessels. We have modified this enzyme in a manner that will increase the enzyme activity on the surface of platelets and on the cells that line the blood vessel wall. We will thoroughly study this new drug by performing experiments in the laboratory as well as by studying its effect in mice.Read moreRead less