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.
The Role Of SKAM And Sphingosine Kinase In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$281,340.00
Summary
Many aspects of wound healing are poorly understood. We have identified a novel cellular pathway that appears critically involved in controlling wound contraction. This project aims to characterise this cellular pathway to understand the exact mechanisms whereby it controls this critical aspect of wound healing. With this information we will develop topical therapeutics to aid the wound healing process.
I am a cell biologist determining how the organization of the plasma membrane influences signal transduction processes; my long-term goal is to understand the spatial–temporal organization of cell signalling.
Pre-clinical Assessment Of The Therapeutic Potential Of Targeting The Hippo Pathway In Muscle Wasting & Muscle-derived Cancer
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Recent findings have identified the Hippo signalling pathway as an important regulator of processes in muscle fibres and muscle progenitor cells. This project will look at the significance of the Hippo pathway in the development of muscle wasting caused by statin administration, and in the genesis of muscle derived tumors (rhabdomyosarcoma). The studies will determine if interventions that regulate the Hippo pathway could provide new therapies for these important muscle-related diseases.
Fzd receptors are often upregulated in gastric cancer, and recent studies have shown that targeting these receptors has be effective at reducing cancer cell growth in other cancers including prostate and breast. This project will use cutting edge technology to firstly determine the specific requirement for Fzd receptors during gastric cancer and then determine the therapeutic benefit of using an antibody to target these receptors in mouse models and human gastric cancer cells.
Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Suppressor Of Cytokine Signalling (SOCS4) Is A Critical Regulator Of The Anti-viral Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The SOCS proteins are negative regulators of cytokine signalling and immune cell development and function. SOCS4 is the last remaining SOCS protein for which there is no described function or intracellular target. We intend to use well-defined acute and chronic viral disease models, and investigate the role of SOCS4 in infection in order to unravel its function. We will also search for its binding partners and intracellular targets, and determine the signalling pathways regulated by SOCS4.
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem cells.
Characterisation Of Notch Asparaginyl Hydroxylation By FIH-1.
Funder
National Health and Medical Research Council
Funding Amount
$307,841.00
Summary
Cells within our body receive numerous signals telling them when to grow, when to turn into another cell type and exactly what type, and even how to respond to situations like low oxygen. These signals and cells response are very important during embryonic development, when these signals cause a single cell to become a complete person, and also in adults. Here in the embryo, and also in adults, stem cells are very important because they can become many different kinds of cells, depending on what ....Cells within our body receive numerous signals telling them when to grow, when to turn into another cell type and exactly what type, and even how to respond to situations like low oxygen. These signals and cells response are very important during embryonic development, when these signals cause a single cell to become a complete person, and also in adults. Here in the embryo, and also in adults, stem cells are very important because they can become many different kinds of cells, depending on what the body needs. When the signals don't work properly, they cause major problems and diseases, from birth defects, to cancer. Notch is an important protein involved in receiving and passing on certain signals, and is found in organisms as diverse as worms and humans. It tells cells, especially stem cells and other similar cells, when and how to change from one type of cell to another. For example, it is very important in the generation of many different types of blood cells from a single precursor cell. Notch has also been implicated in human diseases such as cancer, where signalling goes wrong and cells keep multiplying out of control, and also certain types of heart disease. Another protein, called FIH, is an oxygen sensor that signals to the cell when there is not enough oxygen around. FIH has also been implicated in cancer and heart disease. We have recently found evidence suggesting that FIH can also influence the activity of the Notch proteins. This means that oxygen levels can potentially have an effect on stem cells and other processes controlled by Notch, and may be very important in cancer and other diseases. This project will first confirm the connection between FIH and Notch. There are a number of different Notch proteins, so we will see if this connection works with all of them. It will also try and work out the consequence of this connection is and how important it is. Finally, the likely biological consequences on human diseases, specifically cancer.Read moreRead less