Analysis Of The Osteoclast Methylome For Characterisation Of Epigenetic Mechanisms Underlying Metabolic Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$299,018.00
Summary
A large number of genetic variants have been identified that have a role in osteoporosis, however for many of these, the mechanism by which they influence the disease remains to be determined. This study will fill a critical knowledge gap by investigating the epigenetic control of gene expression in osteoclasts (bone resorbing cells). This research will generate a unique international resource that will provide foundation data to understand and treat this prevalent and debilitating bone disease.
Genetic testing of IVF embryos promises to improve success but shows no effect of live-birth rates. Many embryos are mosaic: containing cells with correct and incorrect chromosome numbers. Current testing is an invasive biopsy which fails to diagnose how many cells are abnormal in the cells that develop into the baby. Here we will use imaging to determine the ratio of abnormal:normal cells resulting in a non-invasive diagnostic that will improve IVF success.
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.
Harnessing Macrophage-derived Cytokine Signalling In Skeletal Muscle Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$991,926.00
Summary
We propose to develop novel therapies and tissue engineering approaches for the treatment of muscle injury and wasting disorders using specific muscle stem cells called satellite cells. Our ultimate aim is to accelerate the development of safe, effective and affordable muscle stem cell-based therapies, in an attempt to lessen the disease burden of muscle wasting disorders. The approach will make use of the novel stem cell activating compounds and immune cells that we have identified.
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.
Flaviviruses Must Come Of Age: Design Of Stable, Mature Particles By Structural Vaccinology
Funder
National Health and Medical Research Council
Funding Amount
$1,149,487.00
Summary
We have established a powerful toolset combining advanced structural biology and rapid virus engineering that allows us investigate the assembly of flaviviruses in novel ways. This project will integrate these approaches to investigate the role of new ligands that we have identified in the structure of medically-relevant flaviviruses including dengue virus and delineate a novel maturation path for flaviviruses, which will be used to design safer and more effective flavivirus vaccines.
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.
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.
Cryo-EM Inspired Drug Discovery To Treat Human Fungal Pathogenic Infections
Funder
National Health and Medical Research Council
Funding Amount
$987,505.00
Summary
Invasive fungal infections are a major threat to global human health. These are highly prevalent in patients whose immune system is compromised (e.g. HIV, cancer or organ transplant patients). Of growing concern is the rise of new strains of fungal infections that are resistant to at least one of the four drug families being used to treat these infections. Here, we will create new therapeutics that block the activity of an enzyme whose activity is essential for the survival of these pathogens.