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
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.
The Molecular And Biological Roles Of Growth Inhibiting Chromatin Binding Proteins
Funder
National Health and Medical Research Council
Funding Amount
$814,843.00
Summary
Our previous work has led to the identification of mutations underlying human birth defects. Similarly, our proposed work will identify a new gene as potentially mutated in human heart defects. We will determine its overlapping functions with a related gene and elucidate their roles in embryonic development and cancer.
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Determining The Impact Of Inherited Epigenetic Information On Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,691.00
Summary
Recent observations show that the environment in which you live can alter disease susceptibility in your children, without altering the sequence of your genes. This is due to epigenetic mechanisms which control the way the DNA is interpreted. In this study we will study the potential for epigenetic mechanisms to affect sperm production and impact characteristics and disease in the next generation.