Akt Kinase Signalling, Regulated Vesicular Transport And Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$337,850.00
Summary
How do metabolic cues tell cancer cells to make more membranes, or fat cells to make more fat? These are some of the questions that underpin this project, which explores the link between cell signalling, protein trafficking and fat metabolism. Specifically, we aim to define the role of an important signalling molecule (Akt) in intracellular transport and activation of a key integrator of fat metabolism (SREBP). This work will have wide-ranging implications for human health and disease.
In Vivo And Biochemical Appraisal Of Mitochondrial STAT3
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
The Signal Transducer and activator of transcription 3 (STAT3) protein is over-expressed or activated in most cancers. The paradigm for STAT3's role in cancer is that it drives the expression of genes which support tumour growth. Recently I found that STAT3 controls the altered metabolic state required for cancer progression, both by control gene expression and by entering the mitochondria. I propose define the mechanism of STAT3 mitochondrial activity and then translate these findings into anim ....The Signal Transducer and activator of transcription 3 (STAT3) protein is over-expressed or activated in most cancers. The paradigm for STAT3's role in cancer is that it drives the expression of genes which support tumour growth. Recently I found that STAT3 controls the altered metabolic state required for cancer progression, both by control gene expression and by entering the mitochondria. I propose define the mechanism of STAT3 mitochondrial activity and then translate these findings into animal models of cancer.Read moreRead less
Is Mitochondiral STAT3 Necessary For K-Ras Induced Myeloid Leukaemias?
Funder
National Health and Medical Research Council
Funding Amount
$425,326.00
Summary
Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dep ....Myeloid leukaemia (ML) is a family of diseases characterized by the expansion of white blood cells, leading to death from haematopoietic complications. One common mutation that gives a proliferative advantage in ML is in the Ras oncogenes. We recently showed that signal transducer and activator of transcription 3 (STAT3) is necessary for the transforming potential of Ras due to its ability to support the metabolic changes necessary for tumour growth. This research will characterize the STAT3-dependent metabolic changes in ML.Read moreRead less
ACTIVATION OF ISLET INFLAMMATION BY CYTOKINE SIGNALING IN PANCREATIC BETA CELLS
Funder
National Health and Medical Research Council
Funding Amount
$406,838.00
Summary
Type 1 diabetes affects up to 4.7 million people world-wide and its incidence is increasing. It is the result of killing of insulin-producing pancreatic beta cells by cells of the immune system. This project aims to understand how immune cell invasion of the pancreas can become worse because of protein interactions that occur within beta cells, and how these cells can contribute to their own demise.
Inhibition Of AMPK Signalling As A Strategy For Decreasing Appetite
Funder
National Health and Medical Research Council
Funding Amount
$644,266.00
Summary
The enzyme AMP-activated protein kinase (AMPK) has previously been implicated in mediating increased food intake in response to fasting and the appetite-inducing hormone ghrelin. In this study we propose to investigate whether inhibition of AMPK has promise as a strategy to reduce hunger in the context of dietary restriction and increases in energy expenditure, such as exercise. We will also test whether a new AMPK inhibitor has the potential to reduce appetite signalling in cells and in mice.
The key goal of my research is to understand the role of protein phosphorylation in controlling metabolism, with a special emphasis on the structure and function of members of the AMP-activated protein kinase (AMPK) pathway. This is important because the function and survival of all organisms is dependent on the dynamic control of energy metabolism, with energy demand matched to energy supply.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Control Of Anabolic And Catabolic Pathways By AMPK
Funder
National Health and Medical Research Council
Funding Amount
$946,402.00
Summary
This project focuses on the role of the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) in the control of glucose and fat metabolism. AMPK has been linked to the regulation of exercise capacity, longevity and the control of insulin sensitivity. This is important for our understanding of the metabolic dimensions of our Nations most important health problems including, type-2 diabetes, cardiovascular disease, obesity, neurodegeneration as well as other age onset diseases.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.