We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Generating multi-component scaffolding to influence the differentiation of embryonic stem cells. Nervous system diseases are debilitating and will develop in over 50 per cent of people at some time in their life. This project will develop strategies so that stem cells can be utilised to encourage brain repair for the treatment of Parkinson's disease. The technology developed will also be of benefit for the treatment of other nervous system disorders.
Discovery Early Career Researcher Award - Grant ID: DE180100775
Funder
Australian Research Council
Funding Amount
$368,446.00
Summary
Using nanostructured scaffolds to understand and engineer neuronal circuits. This project aims to understand the formation of neuronal circuits in the brain. While the role of biochemical features in the brain is well understood, it is not clear how the biophysical properties of the brain affect circuit formation. The outcomes of this project will improve our understanding of neuronal circuit formation as well as provide design rules for creating scaffolds to repair neuronal circuits after brain ....Using nanostructured scaffolds to understand and engineer neuronal circuits. This project aims to understand the formation of neuronal circuits in the brain. While the role of biochemical features in the brain is well understood, it is not clear how the biophysical properties of the brain affect circuit formation. The outcomes of this project will improve our understanding of neuronal circuit formation as well as provide design rules for creating scaffolds to repair neuronal circuits after brain damage. This project will integrate Australia’s strengths in nanotechnology and neurosciences, bringing Australian research at the forefront of neural engineering.Read moreRead less
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of ....Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of transferring knowledge from biochemistry and biophysics to breeding and agronomy, as CSIRO now has a successful wheat breeding program based on this earlier work of ours. Now that we have discovered a gene that controls water-use efficiency at the leaf level, we wish to see how the gene works, and how it affects mineral nutrition of leaves.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC190100026
Funder
Australian Research Council
Funding Amount
$4,969,663.00
Summary
ARC Training Centre for Cell and Tissue Engineering Technologies. The ARC Training Centre for Cell and Tissue Engineering Technologies aims to provide training to create a highly skilled workforce for the tissue engineering and regenerative medicine sector and to enhance research performance and innovation in Australia through fundamental and applied research carried out in industry-led PhD projects. The research aims to address major aspects of the manufacturing and commercialisation pathway an ....ARC Training Centre for Cell and Tissue Engineering Technologies. The ARC Training Centre for Cell and Tissue Engineering Technologies aims to provide training to create a highly skilled workforce for the tissue engineering and regenerative medicine sector and to enhance research performance and innovation in Australia through fundamental and applied research carried out in industry-led PhD projects. The research aims to address major aspects of the manufacturing and commercialisation pathway and barriers faced by the sector, namely improving process efficiencies, enabling early-stage scale-up (cell/tissue) and development of the sector's supply chain. The knowledge created and research undertaken would help to accelerate commercialisation in regenerative medicine, tissue engineering and cell therapies.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less