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.
Matching Supply And Demand: How Does Metabolism Fine-tune Signal Transduction?
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Insulin controls nutrient traffic and disrupting its actions are linked to many diseases: type 2 diabetes, cancer, heart disease. Here, I will test a novel hypothesis that our cells’ metabolic rate, defined by the balance between nutrient supply and energy expenditure, controls how cells respond to insulin. These metabolic regulatory nodes would play a major determinant of many essential functions linked to human health, and thus provide novel therapeutic targets for numerous diseases.
Metabolic Wiring In Adipocytes - Unique Role In Maintaining Long-term Health
Funder
National Health and Medical Research Council
Funding Amount
$1,077,886.00
Summary
Fat cell metabolism is wired to optimize the cell’s ability to make and store lipid while programming the cell to fulfil its function in whole body metabolism. We will: 1) map fat cell metabolism under optimal and insulin resistant conditions; 2) explore the role of 3 nodes in his metabolic circuit predicted as control points; 3) use a novel genetically engineered mouse model to explore the functional significance of fat cell metabolism in whole body insulin sensitivity.
Chemerin, A Novel Therapeutic Target For Modulation Of Adipose Tissue Mass
Funder
National Health and Medical Research Council
Funding Amount
$535,621.00
Summary
Obesity is a significant public health issue due to its increasing prevalence and association with other diseases including cardiovascular disease. Efforts to pharmacologically prevent and treat obesity are impaired by an incomplete understanding of the genes and metabolic processes involved. This project will use cell and animal models to examine the processes that occur during the expansion of fat tissue which will broaden our understanding of obesity and assist in identifying new therapies.
Most common diseases of ageing like diabetes and cancer have proven intractable because much of our knowledge is limited to individual molecules. This proposal takes a global approach to complex diseases, utilising quantitative high-resolution methods and computational modelling. This research will lead to a completely new way of thinking about complex diseases providing a range of completely novel treatment options.
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.