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Targeting The Crosstalk Between Metabolism And Epigenetics To Treat Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,032,259.00
Summary
Virtually all liver disease related morbidity and mortality is a consequence of fibrosis that culminates in liver failure or liver cancer. Since anti-fibrotic drugs are not available, new approaches to drug development are required. We have discovered a novel strategy for such drug development by modifying the expression of a specific gene (RARRES1) in a highly targeted manner and thereby interrupting the energy production that is needed by cells to drive fibrosis.
Crossing A Frontier In Cardiac Fibrosis: A Single-cell Multi-omics Approach To Understanding Fibroblast Agency In Models Of Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,199,254.00
Summary
Cardiovascular disease is the most serious cause of mortality and morbidity in society, with one Australian dying every 13 mins. Our focus is on cardiac fibroblasts - changeable cells that regulate the mechanical integrity of the heart, and which are key therapeutic targets in heart disease. Single cell methods have revolutionised the study of complex tissues. Here we will apply molecular assays to thousands of single heart cells to build a new conceptual framework for fighting heart disease.
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
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.
Reprogramming Human Fibroblasts Into Induced Trophoblast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$889,064.00
Summary
We have been able to generate artificial human trophectoderm which is the tissue that creates the placenta. This will allow us to do research in how the genes control the fate of these cells without the need of human embryos or placenta. We anticipate that the derivation and characterising these cells will revolutionise placenta research, which in turn will contribute to the establishment of new therapies for placenta disease and infertility.
Advancing The Spatial Analysis Of Cells In Tissues To Profile The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$187,918.00
Summary
Tumours are composed of a mix of different cells, including cancer cells, immune cells and other cells supporting tumour growth. These cells are not organised randomly, but rather are distributed in specific patterns. Here we will develop computational methods to detect these patterns and determine what statistical tests should be used to compare samples. This project will give us the tools to investigate how the location of cells in tissues relates to treatment response and survival.
Stopping Breast Cancer Progression By Targeting Tumour Stroma
Funder
National Health and Medical Research Council
Funding Amount
$772,877.00
Summary
Our latest research demonstrated that CRELD2 protein that is secreted by breast cancer cells alters normal cells surrounding tumour. CRELD2 represents an ideal therapeutic target as it is not important for normal cells and it is a secreted protein and thus can be targeted by numerous means. Successful completion of this research proposal will provide foundation to find new targets for combining therapies affecting both tumour and it's altered environment in breast and potentially other cancers.
Understanding The Molecular Mechanisms Of Cell Death In Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$643,856.00
Summary
Radiotherapy (RT) is responsible for 40% of cancer cures. New technology enables RT delivery in fewer treatments using higher radiation dosages through a technique called 'ART'. While ART is effective in the clinic, the underlying mechanisms of cancer cell death are unclear. Here we show that ART induces two distinct waves of cancer cell death. We will characterize these waves of cell death and determine how to enhance tumour cell killing with pharmacological intervention.
Dendritic Cells Govern The Balance Between Immunity And Homeostasis To Inhaled Antigen
Funder
National Health and Medical Research Council
Funding Amount
$816,131.00
Summary
The development of better intranasal vaccines hinges on the improved understanding of how the immune response is initiated following vaccine delivery into the upper airways. In this project we will provide fundamental understanding of how immune responses to inhaled antigens are regulated; this considerable conceptual advance will lay the foundation for which new intranasally delivered immunotherapies will ultimately emerge.
Characterisation And Targeting T Cellular Metabolism To Improve Control Of Chronic Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$791,427.00
Summary
CD8+ T cells are the frontline warriors of our immune system that can eliminate infected or cancerous cells. However, diseases caused by overwhelming viral infections are associated with widespread impairments in immunity and cellular metabolism. Here, we propose to examine molecular pathways involved in cellular metabolism that could be utilized to improve therapies against viral infection and cancer.