Birth defects can have devastating consequences for individuals and their families, and improving our ability to diagnose and screen for these disorders has implications for treatment and reproductive options. We are using the mouse as a model to discover genes important in a new class of birth defects caused by dysfunction of a hair-like cellular projection known as the cilium.
The Lililwan Project: Prevalence Of Fetal Alcohol Spectrum Disorders In The Fitzroy Valley
Funder
National Health and Medical Research Council
Funding Amount
$777,758.00
Summary
Alcohol use in pregnancy is widespread in Australia. Alchohol may cause physical and developmental problems in the developing child including the Fetal Alcohol Spectrum Disorders (FASD). This collaborative project, initiated and led by Aboriginal leaders in the Fitzroy Valley in the remote East Kimberley, WA, will establish the prevalence of FASD, health and developmental problems in a population of primary school-aged, predominantly Aboriginal children and develop strategies for service deliver ....Alcohol use in pregnancy is widespread in Australia. Alchohol may cause physical and developmental problems in the developing child including the Fetal Alcohol Spectrum Disorders (FASD). This collaborative project, initiated and led by Aboriginal leaders in the Fitzroy Valley in the remote East Kimberley, WA, will establish the prevalence of FASD, health and developmental problems in a population of primary school-aged, predominantly Aboriginal children and develop strategies for service delivery, prevention and education.Read moreRead less
Mediator Kinase As A Therapeutic Target For Wnt/β-catenin Dependent Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$949,907.00
Summary
Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy ....Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy.Read moreRead less
Understanding The Role Of SSB1 In Embryonic Development And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Normally DNA exists as a double helix where two strands are zipped together. When single-stranded (ss) DNA is exposed during various cellular processes it can be easily damaged and degraded by cellular enzymes, but is protected by ssDNA binding proteins (SSBs). We have identified two new SSBs (SSB1 and SSB2) that play a crucial role in DNA repair and will investigate the role and physiological function of these important proteins.
Determining The Impacts Of Epigenetic Modifying Drugs On Germline Programming And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$863,918.00
Summary
New drugs have been developed that inhibit specific enzymes that regulate epigenetic pathways in cells. These pathways significantly affect growth and development in offspring and may represent a risk to future children of patients taking the drug. This project will determine these risks and provide data for developing clinical guidelines for safe use of the drugs.
Molecular Mechanisms Of Testosterone Action On Midbrain Dopamine Neuron Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$339,739.00
Summary
Schizophrenia is characterized by psychosis, social and occupational dysfunction and cognitive deficits. Males are more often diagnosed and more severely impaired than females. Onset in males is most frequent during adolescence, a time of increasing sex hormones. We ask, how do sex hormones act on the adolescent male brain to impact the onset and symptoms of schizophrenia? The answer will allow development of gender and age-specific interventions to prevent onset or ameliorate symptoms.
Gene Identification In Familial Orofacial Clefts By Genomic Technologies
Funder
National Health and Medical Research Council
Funding Amount
$565,181.00
Summary
Cleft lip/palate (CL/P) is among the most common malformation disorders but the causes of this condition are largely unknown. We do know that gene mutations cause CL/P in some people. We have also shown that the p63 gene may influence the activity level of genes involved in CL/P by attaching to regulatory elements near these genes. Changes in as yet unidentified genes controlled by p63 are strong possibilities for the cause of CL/P. We will test these by next generation sequencing, a technique t ....Cleft lip/palate (CL/P) is among the most common malformation disorders but the causes of this condition are largely unknown. We do know that gene mutations cause CL/P in some people. We have also shown that the p63 gene may influence the activity level of genes involved in CL/P by attaching to regulatory elements near these genes. Changes in as yet unidentified genes controlled by p63 are strong possibilities for the cause of CL/P. We will test these by next generation sequencing, a technique that analyses all human genes.Read moreRead less
While there has been recent excitement about possible treatments for the symptoms of Autism, advances in understanding the underlying neuroscience of abnormal brain function that underlies autistic tendency are still painfully slow. This application aims to establish fully a physiological mechanism for altered autistic perception, to see if it can be applied to early diagnosis in infants and young children and to establish whether in such plastic young brains it is possible to guide perceptual l ....While there has been recent excitement about possible treatments for the symptoms of Autism, advances in understanding the underlying neuroscience of abnormal brain function that underlies autistic tendency are still painfully slow. This application aims to establish fully a physiological mechanism for altered autistic perception, to see if it can be applied to early diagnosis in infants and young children and to establish whether in such plastic young brains it is possible to guide perceptual learning to permanent improvement.Read moreRead less
Periconceptional Alcohol Exposure: Effects On The Embryo And Fetus And Disease Risk In Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
It is known that consuming large amounts of alcohol during pregnancy can have deleterious effects on fetal growth and development. Less is known about the effects of consumption of alcohol just around the time of conception. This project will use animal models to explore if alcohol can alter development of the very early embryo and whether this has long term consequences for the health of offspring after birth.
Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.