Defining The Molecular Effectors Of Gene/environment Interaction On Mouse Heart Development
Funder
National Health and Medical Research Council
Funding Amount
$749,271.00
Summary
One third of all birth defects involve the heart, and are the most common cause of infant death. Some defects are due to genetic factors, but others arise when the pregnant mother is exposed to environmental stress. We will examine how one stress (low oxygen levels) causes abnormal heart formation in the embryo, look at what causes this at a molecular level, and explore if such stress increases the risk of heart defects in families with a history of such abnormalities
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
Bone Marrow Macrophages: “Resident Evil” In The Establishment And Progression Of Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$570,585.00
Summary
Multiple myeloma (MM) is a cancer that develops within the bone marrow (BM). To date, which cells of the BM stroma are required for the support of MM growth remains unknown. Our preliminary data suggest BM resident macrophages, expressing CD169 and CX3CR1, are essential for MM growth. Using innovative and elegant animal models of MM, we will define the role of these macrophages in MM growth and determine if macrophage-targeted therapies can delay MM growth in the relapsed disease setting.
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Defining The Mechanism Of Assembly Of Herpes Simplex Virus In The Neuronal Growth Cone And Its Subsequent Exit To Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$774,624.00
Summary
Herpes simplex virus (HSV) causes dormant infection of nerve cell bodies near the spine. It periodically reactivates to be transported along nerves to the skin where it causes oral, genital or neonatal herpes and mediates HIV superinfection. HSV assembles into its final form in the terminal part of the axon just prior to crossing into skin. Elucidating the mechanism of HSV assembly and exit will facilitate new strategies for antiviral agents and immune treatment for HSV and similar viruses.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
The Intrarenal Renin Angiotensin System (RAS) In Indigenous Women: An Early Indicator Of Renal Dysfunction In Women At Risk Of Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$645,358.00
Summary
Indigenous women are twice as likely to have low birth weight babies compared to non-Indigenous women and 2.5 times as likely to develop preeclampsia, possibly because they have a much greater incidence of chronic kidney disease, predisposing them to these pregnancy outcomes. We have found a new, sensitive marker of early stage renal dysfunction in pregnancy that could be useful for detecting early stage renal disease and which is indicative of an increased risk of adverse pregnancy outcome.
A Population-based Birth Cohort Study Of The Development Of Atherosclerosis In Early Life
Funder
National Health and Medical Research Council
Funding Amount
$780,067.00
Summary
Cardiovascular disease (heart attack and stroke) are leading causes of death and illness in adults in Australia. The changes in blood vessels that lead to these conditions begin before birth. This project investigates the factors that contribute to these early changes from birth onwards, and will facilitate development of targeted prevention in high-risk groups to reduce cardiovascular disease in later life.