Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normal ....Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normally controlled and how it can be manipulated industrially. This should provide significant benefits, impacting stem cell biology (improving stem cell production), tissue engineering (improving growth of artificial tissues), veterinary science and agriculture (improving productivity).Read moreRead less
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
The pathology of many acute and chronic diseases associated with the inappropriate activation of genetically encoded programmed cell death pathways, such as sepsis, stroke, diabetes and neurodegeneration, is linked to detrimental inflammation. This project will accurately define at the molecular level how programmed cell death triggers inflammatory responses, and use this knowledge to test novel and next-generation therapeutic strategies in inflammatory-driven diseases.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
The Role Of Cell Death Pathways In Inflammation And Pathogen Infection
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Cell death and inflammation are essential for protection against pathogen infection but can also cause human diseases. Inflammation caused by the IL-1? protein has been implicated in diseases such as type II diabetes, arthritis and cancer. This project aims to elucidate how IL-1? protein activity is regulated at the molecular level. It also seeks to understand how the pathogen responsible for Legionnaires’ disease manipulates cell death to allow for successful invasion of the human host.
The Emergence Of Dead Enzymes As Signal Transducers And Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
The cells within our bodies are constantly being replenished by new cells. Removal of old cells is typically fast and without fanfare. However, in some cases, cell death can be used to evoke an inflammatory response. My work examines the molecular details of how this happens and how we might advance our knowledge to develop novel drugs to prevent inflammatory diseases, such as Crohn's disease and psoriasis.
Testing A Combination Of 2 Clinical Drugs, An IAP Inhibitor And P38 Inhibitor, To Treat AML
Funder
National Health and Medical Research Council
Funding Amount
$200,890.00
Summary
Current treatments only cure 50% of Acute Myeloid Leukaemia (AML) patients, and novel approaches to treatment are desperately needed to improve survival of patients with leukaemia. One new drug, Birinapant, is currently being tested in clinical trials to treat AML. I have found that some AMLs are resistant to Birinapant treatment but the addition of a second drug (called “p38 inhibitors”) can now overcome this resistance. I will test how effective combining these two drugs can be to treat AML.
Cells are building blocks of living things and require signalling pathways to communicate their functions. We discovered a new signalling pathway in flies that remarkably exists in yeast and plants to more complex organisms like mice and man. We will study this new signalling pathway in flies to find out how and why it communicates in cells. As flies and humans share similar genes, our studies will inform how this previously unknown signalling pathway functions from simple to complex organisms
Regulation Of Interleukin-1? Activation In Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
IL-1? protein is required to combat infection but also contributes to inflammatory diseases, such as Rheumatoid arthritis and diabetes. Understanding how IL-1? is produced is therefore critical to the development of better therapeutics for these conditions. We have identified a new pathway involving the protein RIP3 that can cause IL-1? activation. This project will examine how this pathway is molecularly regulated and determine its importance in inflammatory disease models.
Mapping The TNF Pathway: A Qualitative And Quantative Molecular Analysis Of The Components And Post-translational Modifications Involved In Physiological And Pathological TNFR1 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$636,258.00
Summary
TNF is a master regulator of the inflammation response and dysregulated TNF signalling causes many human diseases. We will use a cutting edge mass spectrometry technique that we have developed to analyse molecules required for TNF signalling. Understanding how the TNF signalling works in all cell types and with different forms of ligands will open up therapeutic opportunities to selectively target TNF signalling in inflammatory diseases, such as Rheumatoid Arthritis and Cancer.