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.
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.
Interplay Between Metabolic Reprogramming And Oncogenic Signalling In The Cellular Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$654,035.00
Summary
Chemotherapy resistance is a major barrier to the treatment of triple-negative breast cancer (TNBC). We seek to uncover an intimate link between cell metabolism and oncogenic signalling pathways in regulating the cellular response to chemotherapy. Our studies will identify a critical mechanism limiting the therapeutic efficacy of chemotherapy and investigate combination therapy strategies that could improve the treatment of TNBC.
Identifying The Critical Components Of Growth Factor-mediated Survival Pathways
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
The regulation of cell lifespan (cell survival) is controlled by growth factors and lies at the heart of all biological processes. However, little is known of the molecular switches inside cells that either turn survival on or off. We propose to identify and characterize the molecular switches inside cells that control the balance between cell survival and death. Targeting specific components of these switches may provide new approaches for the treatment of cancer and infectious diseases.
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.
The Role Of Protein Kinase C Epsilon In The Generation Of Lipid-Induced Insulin Resistance In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can in ....Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can interfere with the normal signalling of insulin. We have recently found that mice lacking an enzyme thought to be involved in such negative pathways are less susceptible to insulin resistance caused by high-fat feeding. The aim of this project is to investigate the mechanism by which this enzyme contributes to inhibition of insulin action. We will determine the step in normal insulin signalling which is blocked by the activation of the enzyme upon increased fat supply. This will help us to determine the pathway leading from the enzyme to insulin signalling. We will also identify the particular form of fat which leads to activation of the enzyme. This work will lead to a better understanding of the mechanisms by which fats can play a role in the generation of insulin resistance, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.Read moreRead less
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.
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.