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.
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.
The Relationship Between Genes, Environment And Oral Disease In Childhood - A Study Of Twins
Funder
National Health and Medical Research Council
Funding Amount
$88,766.00
Summary
Half of Australia's children suffer tooth decay, placing them at risk of toothache, infection and hospitalisation, as well as a host of other problems like sleeping, eating and concentrating. Current preventive strategies are failing, due to an incomplete understanding of the causes of decay. This study of twins, who have been followed since pregnancy, will help to explain the role of genetics as well as other factors such as maternal and early childhood illness in dental disease.
Whole Genome Pharmacogenomics Study Of Susceptibility Of Birth Defects In Children Born To Mothers Taking Anti-Epileptic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$663,160.00
Summary
This project will investigate for genes that determine why certain women have an increased risk of having a baby with a birth defect if they become pregnant while being treated with a medication for epilepsy. Subjects will be recruited from the Australian Pregnancy Register, the findings validated using subjects from the UK Epilepsy and Pregnancy Register. The study will comprehensively examine for both common and rare changes in genes across the entire human genome.
Mechanisms Underpinning The Epigenetic Code And The Role Of Histone Variants
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
A fundamental unanswered question in biology is how a single fertilized mammalian cell can differentiate into a multicellular organism when every differentiated cell type inherits the same DNA. Fundamental to this development process is that different sets of genes are expressed in different cell types. This investigation will show that a key mechanism to regulate gene expression is the way our DNA is covered with specifically modified and altered forms of histone proteins.
How The Dosage Of A Down Syndrome Candidate Gene Affects Neural Circuitry And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$414,961.00
Summary
In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.
Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
Conditional Knockout Of The Murine Patched Gene For The Study Of Skin Differentiation And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectiv ....Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectively removing patched gene function from specific cell of the skin. In doing this we will be able to determine the exact role of this gene in skin development, and how mutation causes common skin cancer.Read moreRead less
The Downstream Targets Of Patched/Hedgehog Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$423,055.00
Summary
The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which ....The patched-hedgehog gene pathway is disturbed in common human cancer, including basal cell carcinoma of the skin, medulloblastoma, rhabdomyosarcoma and ovarian fibroma. This application proposes to look at the genes turned off and on by the patched gene. By identifying these genes and examining their function we will identify the exact genetic disturbance which results in a large proportion of common human cancer. Once we find these genes this opens up the possibilities of designing drugs which specifically block the action of the geneticdefect and thereby treating the tumours.Read moreRead less