Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.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
Mechanisms Underlying Generation Of Febrile Seizures In Mouse Models Of Human Familial Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$304,559.00
Summary
Febrile Seizures (FS) affect 3% of children aged 0.5 - 6 yrs and have been proposed as an indicator of severe forms of adult generalized epilepsy. Mechanisms underlying FS generation are unknown although studies of Australian families suffering from epilepsy have linked 2 genes to FS. We have generated mice expressing these 2 genes. Aims and Outcomes: to investigate events triggering FS which will provide important insights into why FS occurs in children. (NB: CIA 2 yr career interruption)
Prevalence report by the Australian Advisory Board on Autism Spectrum Disorders (ASD) estimated that 1 child in every 160 children in the 6-12 year-old age group is affected by ASD. There is no cure for ASD and the causes are not understood. We propose that sex hormones may play a role in the development of these disorders. We will test this hypothesis using knockout and transgenic mouse models which have social interaction deficits and brain structure reminiscent of these disorders.
Relaxin-3/RXFP3 Signalling And Regulation Of Affective Behaviour _ Studies In Normal/transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Mental illness is a significant social and economic burden worldwide and knowledge of the underlying causes and more effective therapies are required. Our research aims to use pre-clinical animal models to characterize a little studied brain neuronal network implicated in control of arousal and stress, which could lead to improved treatment of psychiatric disorders such as depression.