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An Integrative Approach To Define And Attenuate Genomic Risk Of Coronary Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$988,454.00
Summary
One in four individuals that have a heart attack do not have traditional risk factors such as high blood cholesterol levels. This highlights the importance of 'family history', which we can now quantify as 'genetic risk'. These studies will determine (i) which genes are important in contributing to this genetic risk (ii) how these genes change biological pathways to increase risk and (iii) the effectiveness of modulating these biological pathways to reduce the risk of heart disease.
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.
Finely Tuned Glutamate Receptor Inhibitors As Novel Therapeutics For Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$1,168,829.00
Summary
Neurodegenerative disorders are among the leading causes of death and disease burden. New drugs are needed to treat both symptoms and disease progression. This project aims to understand the properties of different drug-like compounds to inhibit proteins on the surface of brain cells (glutamate receptors) to impact disease progression and symptoms in a preclinical disease models. The project will yield a better understanding of how best to target glutamate receptors for therapeutic effect.
Novel Genetic Tools For Tracking The Origins And Spread Of Plasmodium Vivax
Funder
National Health and Medical Research Council
Funding Amount
$536,158.00
Summary
Plasmodium vivax causes >8 million malaria cases annually. Containment of this parasite is constrained by limited surveillance tools. This project will establish genetic data on >6,000 P. vivax cases from across the globe. Using this data, we will develop an online platform with analytical tools to identify the main reservoirs of infection, how parasites are spreading within and across national borders, and how effectively interventions have impacted on parasite transmission.
How A Multidrug Resistant Bacterial Pathogen Has Become Pandemic
Funder
National Health and Medical Research Council
Funding Amount
$1,116,544.00
Summary
The pandemic spread of antibiotic resistant E. coli ST131 is a major human health problem. ST131 is the globally dominant cause of urinary tract and bloodstream infections. This project will use advanced genetics and animal infection models to understand the features of ST131 that have fueled its global dominance. The outcomes will unravel the molecular mechanisms that enable ST131 to persist and cause repeat infection, and guide the development of new precision medicine therapeutics.
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.
Growth Factor Directed Developmental And Pathological Lymphangiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$1,048,507.00
Summary
The formation of new lymphatic vessels occurs in normal development and in diseased tissues in cancer and cardiovascular disease. We have developed an understanding of how lymphatics form in development but we understand far less about how they form in disease. This project will apply multidisciplinary approaches, including genetics and computational biology, to compare how lymphatics form in development and disease. We hope to uncover new ways to manipulate this process for therapeutic gain.
Exploring Non-canonical Roles For The Ribosomal RNA Genes Critical For Malignant Transformation And Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$1,972,669.00
Summary
Genes are encoded by linear DNA sequences, and whether they are expressed or silenced will depend on modifications and 3D interactions with other genomic regions. We aim to identify genes that interact with the a subnuclear body called the nucleolus during cancer development and differentiation. Understanding how these 3D genomic interactions are altered for the coordinated expression of a suite of genes may provide the basis for novel strategies to manipulate gene expression in disease.
Shedding Light Onto The Structural Secrets Inside Pluripotent Stem Cells In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$555,890.00
Summary
To meet the challenges of life, a human being requires 30 trillion cells, a blue whale a staggering 100 quadrillion. This vast diversity of cells derives from very few unspecialised cells that can become any cell type of the adult body - the pluripotent stem cells. We will use innovative imaging techniques to uncover the cellular architecture of pluripotency to provide critical insights into how the various parts of a versatile cell, its cytoskeleton and organelles, are assembled in real-time.