Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
Role Of The Drug Metabolising Enzyme Arylamine N-acetyltransferase 1 In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,196.00
Summary
The current project will identify the molecular mechanism(s) that underpins the significant changes in phenotype seen in a range of human cancer cells. The expected outcomes will be to demonstrate that NAT1 is critical for the clearance of pABG in cancer cells. The results will be important in the context of understanding this family of intracellular enzymes and will change the current thinking on the function of the arylamine N-acetyltransferase in normal and cancer cells.
The Role Of GAPDH Acetylation And HDAC6 In Liver Metabolism And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$635,428.00
Summary
Type 2 diabetes (T2D) is characterised by persistent elevated blood glucose levels. Altered liver metabolism is a key contributor to elevated blood glucose levels in T2D, through uncontrolled synthesis and release of glucose. This project will examine whether regulation of a metabolic enzyme called GAPDH by a process termed acetylation, contributes to normal liver glucose metabolism. This project will also assess whether altered GAPDH acetylation contributes to hyperglycaemia in T2D.
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 mechanisms controlling cell growth are often disrupted in cancers. We have identified on such growth control mechanism. When normal body cells are treated with a particular family of drugs known as histone deacetylase inhibitors, they react by stopping proliferating, but will resume normal growth when the drug is removed. However, we have found that similarly treated tumour cells are killed by these drugs. The difference between the normal and tumour cells is the functionality of a particula ....The mechanisms controlling cell growth are often disrupted in cancers. We have identified on such growth control mechanism. When normal body cells are treated with a particular family of drugs known as histone deacetylase inhibitors, they react by stopping proliferating, but will resume normal growth when the drug is removed. However, we have found that similarly treated tumour cells are killed by these drugs. The difference between the normal and tumour cells is the functionality of a particular growth control. The identification of how this growth control mechanism operates in normal cells, and defining the defect in tumour cells has the potential to identify new targets for more specific and potent anti-cancer drugs. The increased specificity, i.e. destruction of only the tumour cells while have little or no effect on the surround normal body tissue, would be extremely beneficial as one of the drawbacks to conventional anti-cancer treatments is their unwanted normal tissue toxicities. This is cause of the many debilitating side effects associated with chemo and radiotherapy which can limit the clinical effectiveness of these treatments.Read moreRead less
Nuclear Sirtuins At The Interface Between Epigenetic Regulation And Human Cytomegalovirus Pathogenesis: A Proteomics Perspective
Funder
National Health and Medical Research Council
Funding Amount
$399,488.00
Summary
Human cytomegalovirus (HCMV) is a human pathogen that infects over 60% of the adult population, and is a major cause of birth defects causing permanent hearing and vision loss, and mental retardation. To investigate the critical involvement of host epigenetic factors, I will study the roles of sirtuins during HCMV infection. Through proteomic, genomic, microscopy, and bioinformatic techniques, I aim to further our understanding of viral pathogenesis, towards developing novel therapies.
The Role Of MOZ In The Development Of The Hematopoietic System, Spleen And Thymus
Funder
National Health and Medical Research Council
Funding Amount
$324,375.00
Summary
Current treatment of leukaemia in adults is unsatisfactory with the majority of patients dying. In the past most treatments for cancer have been empirical, that is a particular drug has been found to be effective by trial and error rather than a process of rational design. In order to improve the rate at which effective treatments for leukaemia are found it is necessary to understand how hematopoiesis is regulated and what the critical points are where things can go wrong, leading to cancer. Som ....Current treatment of leukaemia in adults is unsatisfactory with the majority of patients dying. In the past most treatments for cancer have been empirical, that is a particular drug has been found to be effective by trial and error rather than a process of rational design. In order to improve the rate at which effective treatments for leukaemia are found it is necessary to understand how hematopoiesis is regulated and what the critical points are where things can go wrong, leading to cancer. Some genes are commonly found to be mutated in leukaemia. Clearly these genes are involved in some key aspect of regulation of hematopoiesis. We are studying one of these genes, MOZ, which is mutated in acute myeloid leukaemia. The purpose of this grant is to determine what the normal function of this gene is. One of the most promising new treatments for leukaemia is directly targeting the regulation of gene expression inside the cell. MOZ is one of the proteins, which regulates gene expression in hematopoiesis and controls the differentiation of different types of blood cells. One of the possible effects of these new types of anticancer drugs is to accentuate the normal function of MOZ. However, at the moment we don't know what the normal function of MOZ is so it is impossible to test this prediction. If we know which pathways controlling blood formation MOZ is acting in it may be possible, in the future, to use this information to improve on the current anti cancer drugs in a more directed way than has been possible in the past.Read moreRead less
Do The Mitochondrial Sirtuin Enzymes, SIRT3 And SIRT5, Affect Insulin Action In Skeletal Muscle?
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Metabolic disorders such as obesity, insulin resistance and type 2 diabetes are characterised by inappropriate handling of nutrients. Mitochondria are the primary site for nutrient oxidation in cells. Sirtuins such as SIRT3 and SIRT5 are abundant in mitochondria and may affect mitochondrial function and insulin action in skeletal muscle. Understanding the biochemical pathways involved in energy metabolism in skeletal muscle is crucial in the development of therapies for insulin resistance and ty ....Metabolic disorders such as obesity, insulin resistance and type 2 diabetes are characterised by inappropriate handling of nutrients. Mitochondria are the primary site for nutrient oxidation in cells. Sirtuins such as SIRT3 and SIRT5 are abundant in mitochondria and may affect mitochondrial function and insulin action in skeletal muscle. Understanding the biochemical pathways involved in energy metabolism in skeletal muscle is crucial in the development of therapies for insulin resistance and type 2 diabetes.Read moreRead less