An AMPK Myristoyl Switch Controls AMP Mediated Metabolic Stress Signaling
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project is investigating an enzyme called AMP-activated protein kinase that plays a pivotal role in controlling how our bodies regulate energy metabolism in response to exercise and diet. Improved understanding of how this enzyme is regulated may provide new therapeutic methods for mimicking the beneficial effects of diet and exercise to treat multiple metabolic diseases including obesity, Type 2 diabetes and cardiovascular disease.
After infection with viruses, parasites and bacteria the protein SerpinB2 becomes very abundant in macrophages, which are white blood cells involved in inflammation. Unfortunately, what this protein is doing is very unclear. We have found that macrophage SerpinB2 dampens the responses of other immune cells. This grant aims to determine how this is achieved and thereby help resolve the role of this protein in a number of diseases such as cancer, lupus, asthma and pre-eclampsia.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
This Program studies the mechanisms that control blood cell formation and how abnormalities play a role in leukaemia, a significant health problem worldwide. Despite some improvements, two major problems remain: controlling progression of leukaemia and relapse. The Program tackles these two major issues with the combination of studies of normal blood and leukaemia cell function, drug design and clinical trials ensuring a direct pathway from discovery to patient benefit.
Profiling Global Inflammatory Signatures For GPCRs In Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$687,770.00
Summary
Macrophages are important white blood cells of the immune system. They trigger inflammatory responses to infection or injury, but prolonged inflammatory responses can lead to chronic diseases. In this project we aim to better understand how macrophages sense the outside environment, how external signals trigger inflammatory processes, how this leads to diseases such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases, and how to control them with drugs.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Suppression Of Immunity By The Malaria Parasite Antigen Plasmodium Falciparum Erythrocyte Membrane Protein-1 (PfEMP-1)
Funder
National Health and Medical Research Council
Funding Amount
$96,698.00
Summary
The malaria parasite P. falciparum infects red blood cells and makes the cells put on their surface a protein called PfEMP-1. The parasite can effectively “hide” by constantly changing this protein and making it unrecognizable by the immune system. PfEMP-1 can also suppress the immune system so that it can’t respond adequately to infection. Therefore, understanding PfEMP-1 function is important. I will investigate how PfEMP-1 can do this by looking at its cross talk with the immune system.
Defining The Role Of The Novel Gene MUL1 In Antiviral Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$511,596.00
Summary
Uncontrolled immune responses can clinically manifest in chronic inflammatory disorders. Viral infections carry a significant global health burden, causing acute and chronic inflammation. This study will characterize a novel regulator of anti-viral immune responses. Understanding the regulation of infection models may provide the means of manipulating immune responses to control infections and provide better health outcomes.
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.