Involvement Of The Asciz Gene In Kidney Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$591,128.00
Summary
Congenital abnormalities of the kidney and urinary tract (CAKUT) affect more than 1/500 children. Urogenital development is primarily controlled by a small number of genes that regulate the timing and position of kidney formation. In this application we describe a novel gene involved in this process, establish where it acts, how it regulates gene expression and whether mutations in it cause CAKUT.
Tissue-dependent Proregenerative Mechanisms In Adult Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$638,742.00
Summary
This proposal addresses how immune cells participate in regeneration of damaged organs in adult zebrafish. Unlike mammals, zebrafish have a remarkable capacity to regenerate their various body parts in adulthood, providing a model to understand how regeneration capacity might be induced in humans. The proposed study will define mechanisms of immune-mediated regeneration that could provide new cellular and molecular targets for stimulating replacement of damaged organs in the human injury setting
Epigenetic Regulation Of Male Fetal Germ Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$562,176.00
Summary
Men’s health has declined over recent decades, but the causes remain unknown. Non-genetic (epigenetic) mechanisms affecting formation and function of the male germ cells (which produce sperm) may play an important role. We will determine the role of a key epigenetic modifier on the formation and function of male germ cells, including germ cell tumours. This study will provide fundamental insights into male germ cell epigenetics, and significantly contribute to understanding men's health.
Identifying The Pathological Mechanism Of PCDH19-Girls Clustering Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$523,988.00
Summary
Changes in the PCDH19 gene are a relatively common cause of epilepsy. To better understand the basis of this disorder, we have developed unique mouse models that mimic the genetic changes and symptoms of this condition. We will perform careful analysis of brain development in these models to determine the primary cause of this condition. These experiments will create greater understanding of how changes in PCDH19 cause epilepsy in girls and facilitate the development of new treatments.
Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
Identifying Genes Required For Vertebral Column And Heart Formation
Funder
National Health and Medical Research Council
Funding Amount
$950,418.00
Summary
Birth defects occur in about 3% of live births. These originate as the embryo forms, and we have previously shown that some of these are caused by gene mutation and/or environmental factors during gestation. However, the origins of many such defects remain unexplained. We will examine the DNA of patients to find gene mutations causing such defects. We will also test if mutations in these genes increase the likelihood of the embryo developing a defect if it is exposed to environmental stressors.
Molecular Regulation Of Apoptosis In Endothelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
This project seeks to understand the mechanisms by which cells that make up our blood vessels are kept alive. Impaired blood vessel cell survival contributes to reduced blood vessel health, a major component of cardiovascular disease. Knowledge of how these cells are kept alive could prove useful in treating diseases affecting vessel cell survival, or potentially to combat those diseases that are caused by excessive blood vessel growth.
Women are born with a limited supply of eggs and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. This project aims to shed some light on the mechanisms that control egg supply and reproductive longevity in women by investigating the role of the cell death protein Bid within the ovary.
Effects Of The Histone Acetyltransferases MOZ And QKF On Chromatin Modifications
Funder
National Health and Medical Research Council
Funding Amount
$349,576.00
Summary
Cancer of the blood (leukaemia) can be caused by rearrangements of the genetic material (DNA) that cause fusions between ordinarily separate proteins. Monocytic leukaemia zinc finger (MOZ) fusion proteins cause aggressive leukaemia. We have shown that MOZ associates with DNA packaged with histone proteins into chromatin, changes histones and gene activity. We will examine how MOZ and the closely related QKF protein affect the chromatin to elucidate the function of MOZ and QKF.
Hormonal Responsive Coding And Non-coding Genes In Penile Differentiation And Hypospadias
Funder
National Health and Medical Research Council
Funding Amount
$835,182.00
Summary
Hypospadias, a failure of the correct formation of the penis, is the second-most common birth defect, occurring in around 1% of boys. It causes distress to both newborn and parents, requiring surgical intervention, and is a burden of cost and is a risk to the child. Furthermore, it is frequently associated with other abnormalities. We have a novel model in which we can induce penis abnormalities and define the link between hormonal exposures and defective penis differentiation.