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.
Mitochondrial donation in fertilised eggs is a possible therapy for avoiding mitochondrial DNA disease, but there are major safety concerns, such as mutant mitochondrial carryover. To address these concerns, we will develop two new methods to eliminate carryover risk, then translate our findings to human eggs. Also, we will determine if the mitochondrial donation procedure affects offspring health. Our findings will serve as a guide for adopting the technology.
UNDERSTANDING THE BENEFITS AND LIMITATIONS OF METAPHASE II SPINDLE TRANSFER
Funder
National Health and Medical Research Council
Funding Amount
$1,629,373.00
Summary
Mitochondrial DNA (mtDNA) diseases are transmitted from a mother's eggs to her children. However, the levels of affected mtDNA differ amongst her eggs. Consequently, a carrier would not know if the newborn child were to suffer from these diseases. Mitochondrial Donation offers couples the potential to have an unaffected child. We will undertake the most comprehensive study of mitochondrial donation using one of its associated approaches to determine if it produces healthy embryos and offspring.
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.