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
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.
Does Mobile DNA Activity Contribute To Reproductive Failure?
Funder
National Health and Medical Research Council
Funding Amount
$389,076.00
Summary
One in four pregnancies in Australia will end in miscarriage. Infertility affects about 15% of Australian couples and is highly correlated with increasing maternal age. In this study, we will use cutting edge single-cell genomic approaches to investigate the activity of mobile DNA elements or “jumping genes” as a previously unexplored cause of reproductive failure, including spontaneous miscarriage and age-related female infertility.
Understanding Mitochondrial DNA Segregation And Transmission.
Funder
National Health and Medical Research Council
Funding Amount
$512,449.00
Summary
We inherit our mitochondrial DNA from our mothers. Mutations to mitochondrial DNA can give rise to severely debilitating diseases that can be passed from one generation to the next. The aims of this application are to understand how mutant mitochondrial DNA is selected for; when it affects energy production during development; and to ensure that certain reproductive strategies do not result in the adverse transmission of mitochondrial DNA that will affect subsequent generations.
The Role Of The Actin Remodelling Protein, Flightless I, In Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$568,868.00
Summary
Human embryos possess the remarkable capability to repair wounds perfectly with no scarring, unlike adults for whom major trauma can result in life-long disfigurement and immobility. We have identified a method that may be able to reinitiate the ability to repair wounds perfectly and we will test whether this is the case using animal models of fetal repair.
Systemic Approaches Of Muscle Stem Cell Quiescence And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$532,883.00
Summary
In the repair of injured muscles, after physical exercise, as part of the ageing process, and in muscle disorders, activated muscle stem cells proliferate and differentiate to replace affected tissues. The aim of this project is to apply systemic, genome-wide approaches to identify the gene networks involved in the balance between the differentiation or the self-renewing state of muscle stem cells.
Systemic Approaches Of Myoblast Fusion In Vertebrates
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Myoblast fusion is a poorly understood process of crucial importance during muscle growth and repair. Furthermore, engineered myoblasts can be introduced to fuse with mature muscles, forming a stable hybrid organ within the adults, thus offering novel therapeutic possibilities in the future. In this research, we will undertake the first systemic, genome-wide approach to identify and characterise the gene networks underlying muscle fusion in vertebrates.
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
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.