The Mechanism Of Cell Death In Response To Cytoplasmic DNA, And Its Role In Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$517,897.00
Summary
DNA in mammalian cells is in a structure known as the nucleus. Retroviruses such as HIV generate DNA outside the nucleus in the cytoplasm, and detection of DNA in the cytoplasm can lead to cell death, as a defence. All cells carry the remnants of ancient retroviruses in their nuclear DNA. These are normally inactive but may contribute to cancer when activated. This project investigates how normal cells die with cytoplasmic DNA, and whether a defect in this process promotes development of cancer.
The Regulation Of Pluripotency And Self-renewal In Embryonic And Germline Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$491,767.00
Summary
Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal ....Regulation of self-renewal and developmental potential in embryonic and germline stem cells. The capacity of some stem cells to self-renew and under specific conditions, give rise to all adult cell types, a property known as pluripotency , is the key to unlocking the potential of cell based therapies. The development of stem cell based therapies promises to revolutionize the treatment of many common human diseases. For instance, in neurodegenerative conditions such as Parkinsons disease, normal embryonic stem cells grown in culture could be used to replace the lost or disabled neurons in the patient. Many other conditions including diabetes, cystic fibrosis, myocardial infarction (heart attack) and stroke could potentially be treated with stem cell based therapies. Understanding the molecular regulators that govern establishment and maintenance in culture of stem cell lines derived from embryos and from germ cells is the primary goal of this study. We will use well-established techniques to genetically manipulate mouse embryonic stem cells and embryos to examine the role of a specific gene, NANOG. Named after the Celtic legend of Tir NaNog (land of the ever young). When NANOG was forced to remain active, embryonic stem cells were able to grow in media deficient in factors usually required for self-renewal and did not lose their pluripotency even when treated with chemical agents that usually induce differentiation. Understanding the full capacity of NANOG to influence stem cell self-renewal and elucidation of the underlying molecular pathways regulated by this gene will provide valuable insights into the establishment and manipulation of stem cell lines from embryonic and adult tissues.Read moreRead less
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
DECIPHERING THE ROLE OF FOXP1 IN MAMMARY STEM CELLS AND DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$569,109.00
Summary
Breast (mammary) epithelial cells undergo major changes across developmental stages, including puberty, pregnancy and lactation. This project will focus on the role of the molecular regulator, Foxp1, and how it influences normal mammary maturation. This work will inform whether Foxp1 is critical for controlling the activation of dormant stem cells and if this pathway can contribute to breast cancer formation when disrupted.
Developing A New Treatment Method To Prevent Lymphopenia Associated With Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$435,939.00
Summary
Sepsis or blood poisoning kills more people than breast cancer, prostate cancer and HIV/AIDS combined. It has a huge economic burden, yet there is no proper diagnostics markers or treatment. One of the main reasons for sepsis-mediated mortality is lack of functioning immune system patients. We have been able to elucidate the molecular mechanism of sepsis-mediated immune cell death and through this project, we aim to develop diagnostics and therapy for treating sepsis-mediated immune suppression.
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Dual Targeting Of Myc And Apoptosis Pathways For Improved Blood Cancer Treatment Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$754,685.00
Summary
Cancer cells frequently possess defects in genes called MYC and BCL-2 that control their growth and survival. Our preliminary studies have shown that combining novel reagents that specifically target MYC plus BCL-2 leads to enhanced lymphoma cell killing. In the proposed research, we will further develop these reagents and evaluate their ability to treat blood cancer in mice. We expect our approach will provide new avenues for treating cancer patients that respond poorly to current treatments.
Understanding How Defects In Chromosome Structure Can Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$546,557.00
Summary
The correct folding of DNA is critical to a cell's survival. This is orchestrated by a special class of proteins called the condensins. Defects in condensin lead to aberrant chromosome folding and disease. We aim to understand how condensin folds chromosomes and why mutations in condensin are increasingly associated with disease.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.