Most eye diseases have a genetic contribution, whether rare disorders affecting children such as retinoblastoma or congenital cataracts through to common disorders of older people such as myopia, age-related macular degeneration or glaucoma. We will continue our successful research to find genes that cause these diseases and use this to improve patient care and prevent blindness. We will work out how families can use this genetic information to participate in trials to develop new treatments.
Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood for ....Linking mutant zebrafish phenotypes with their underlying genetic lesions. Zebrafish mutants have been generated with many interesting abnormalities, but to understand these abnormalities, the defective genes must be identified by positional cloning. We seek to identify the defective genes underpinning four mutants. Mutant #562 develops a normal nervous system which then undergoes rapid degeneration. The mutant flotte lotte has abnormal gut development. Two mutants with defective early blood formation will be studied. We will establish techniques for several steps that will be useful for all zebrafish mapping projects. We expect the genetic characterization of these mutants to provide new insights into nerve cell survival, gut development, and blood formation.Read moreRead less
Developing technologies that support the genetic modification of rats. Rats and the mouse play critical roles in medical research. Until recently, the targeted genetic modification of a mammal was limited to the mouse. This was due to a technology that was unique to the mouse: embryonic stem (ES) cells. These cells have not been isolated from any other species. The recent development of animal cloning allows for an alternate strategy for targeting genes. We propose to develop cloning strate ....Developing technologies that support the genetic modification of rats. Rats and the mouse play critical roles in medical research. Until recently, the targeted genetic modification of a mammal was limited to the mouse. This was due to a technology that was unique to the mouse: embryonic stem (ES) cells. These cells have not been isolated from any other species. The recent development of animal cloning allows for an alternate strategy for targeting genes. We propose to develop cloning strategies in the rat that supports the genetic modification of this animal. The development of this technology will bring considerable benefits to the areas of physiological research and drug design.Read moreRead less
Finding The Genetic Causes Of Asthma: The Australian Asthma Genetics Consortium (AAGC)
Funder
National Health and Medical Research Council
Funding Amount
$1,697,639.00
Summary
Asthma is a major burden on individuals and health systems. Despite many decades of research, no major effective new treatments for asthma have emerged recently. We will establish a large international consortium to systematically test nearly all known human genes to identify those that influence asthma susceptibility. We expect to identify pathways not previously implicated in asthma and so lead to a potential breakthrough in the development of more effective treatments.
The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by o ....The Production of Respiratory Cell Lineages from Human Embryonic Stem Cells: Towards a Cell Replacement Therapy for the Treatment of Respiratory Specific Deficits. Embryonic stem (ES) cells are a primitive embryonic cell type that can be maintained and grown in vitro. Mouse ES cells can be instructed to develop into a wide range of specific adult cell types. Research into human ES cells has more recently commenced and has already resulted in the controlled production of specific nerve cells by our group. The following project aims to create respiratory lineages from both mouse and human ES cells. Such an undertaking thus aims to provide a basis for the treatment of respiratory specific diseases such as cystic fibrosis and emphysema.Read moreRead less
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulat ....Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulation of a key copper pump, the Menkes protein, which helps control copper levels in the body and we are using the genetic advantages of the fruit fly Drosophila to discover new genes that regulate Menkes activity and therefore copper levels. These studies could lead to novel therapies for a range of copper-related disorders.Read moreRead less
The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated ....The Molecular Basis of Copper Metabolism in Sheep. The unusual copper metabolism of sheep represents a significant agricultural problem. They are very susceptible to copper deficiency, but readily accumulate copper to toxic levels in the liver leading to fatal liver failure. We propose to elucidate the reason for the copper accumulation phenotype of sheep. We are focussing on WND, a copper transporter responsible for copper excretion into bile. We discovered a novel form of sheep WND designated WNDb to distinguish it from the normal form, WNDa. The experiments outlined are designed to understand the function of both proteins in the sheep and their role in copper sequestration.Read moreRead less
Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approache ....Rapid functional analysis of genes involved in skeletal development. Abnormalities of the skeleton are of enormous clinical significance in terms of both number of individuals affected and the cost of treatment. Data derived from this project will underpin targeted research on the mechanisms of inherited and common diseases of cartilage and bone, yielding novel diagnostic and therapeutic targets. In addition, the improved knowledge of cartilage and bone cell development will inform new approaches for developing stem cell therapies and the production of novel biomaterials for the repair of bones and joints. The outcomes of this study will therefore benefit the full spectrum of society from infants to the aged.Read moreRead less
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.