Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Artificial intelligence algorithms to predict risk of injury in racehorses. This project will address the urgent need for predicting and preventing catastrophic and career limiting limb injuries and cardiac arrhythmias in racehorses due to over (or under) training. Using data from GPS and movement sensors integrated into saddlecloths, artificial intelligence algorithms will convert cumulative data on speed, gait, and stride characteristics during training, along with injury data, into a risk mat ....Artificial intelligence algorithms to predict risk of injury in racehorses. This project will address the urgent need for predicting and preventing catastrophic and career limiting limb injuries and cardiac arrhythmias in racehorses due to over (or under) training. Using data from GPS and movement sensors integrated into saddlecloths, artificial intelligence algorithms will convert cumulative data on speed, gait, and stride characteristics during training, along with injury data, into a risk matrix. Recorded heart rate and ECG data will also be analysed using artificial intelligence to detect early evidence of the development of cardiac arrhythmias. The system will improve racehorse welfare, providing a simple interface to warn trainers when risk of injury becomes high, in order to prevent catastrophic breakdown.Read moreRead less
Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred bree ....Enhancing fertility for the Thoroughbred and Standardbred industries. Enhancing fertility for the Thoroughbred and Standardbred industries. Responding to industry calls for improved methods of detecting and managing infertility in both stallions and mares, this project aims to provide a platform for competitive collaborations between universities, biotechnology companies and horse breeders: the end-users of technological developments in equine reproduction. The Thoroughbred and Standardbred breeding industries contribute over $6.5 billion per annum to the Australian economy and employ thousands of staff across their value chains. However, these industries suffer from breeding program inefficiencies that amount to over $800 million in annual losses. Expected outcomes are novel reproductive technologies and specialised research capabilities that will make the Australian equine industry a global leader.Read moreRead less
Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define ho ....Defining the antiviral effects of Wolbachia in Aedes aegypti mosquitoes. Mosquitoes that carry a bacterium called Wolbachia do not transmit human pathogenic viruses. These mosquitoes are being developed as a biocontrol tool to prevent mosquito-borne diseases. This project aims to define the molecular basis for virus inhibition by Wolbachia. Using unique biological tools including mosquitoes carrying different strains of Wolbachia that do or do not inhibit dengue virus, the project will define how Wolbachia modifies its host to create an antiviral state. The findings will provide insight into how viral pathogens can be suppressed in insect hosts. This may guide future viral disease intervention strategies for diverse areas afflicted by insect-borne viral disease, including human health and agriculture.Read moreRead less
Enhancing the efficiency of equine reproduction: relevant to the Thoroughbred and Standardbred breeding industries. The purpose of this project is to link the equine breeding industry with a major centre of reproductive research at the University of Newcastle. By creating this unique nexus, major efficiency gains will be achieved for this industry that will not only secure its international competitiveness but also significantly enhance its profitability.
Subspecies distribution and virulence of Streptococcus uberis. Streptococcus uberis is a significant cause of bovine mastitis. Attempts to produce a successful vaccine against S. uberis have been hampered by the lack of knowledge of phylogenetic relationships within the species and virulence mechanisms. It is uncertain whether pathogenic strains are clonal or are acquired opportunistically from a diverse population in the environment. This project aims to examine the phylogenetic structure of ....Subspecies distribution and virulence of Streptococcus uberis. Streptococcus uberis is a significant cause of bovine mastitis. Attempts to produce a successful vaccine against S. uberis have been hampered by the lack of knowledge of phylogenetic relationships within the species and virulence mechanisms. It is uncertain whether pathogenic strains are clonal or are acquired opportunistically from a diverse population in the environment. This project aims to examine the phylogenetic structure of S. uberis by multilocus sequence typing and investigate control of virulence gene expression in S. uberis. The information obtained will be used to improve the formulation of a bovine mastitis vaccine developed by RMIT University and Vet Biosearch.Read moreRead less
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
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.