Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is ....Improving and manipulating the immune adjuvant properties of recombinant fowlpox vectors. Unbalanced immune responses may cause or worsen common and important diseases such as infections, allergies, cancers and autoimmunity. Interleukin-4 (IL-4) is the only immune active product or cytokine that safely skews an aberrant immune response to a healing type of response. Fowlpox viruses (FPV) provide safe and effective human vaccines. Engineering FPV to make both a relevant antigen and a cytokine is proprietary technology. With our commercial partner and using experimental mice, we will test the concept that FPV making a model antigen and IL-4 initiate and/or maintain beneficial Type 2 responses. A successful outcome will guide clinical FPV-based vaccine development for the treatment of important human and veterinary diseases.Read moreRead less
Mimetics and small chemical compounds for hemopoietic stem cell mobilisation. This project will result in the design and synthesis of new chemical compounds that could be used clinically to help collect blood stem cells for bone marrow transplantation. For patients this will mean more effective and less painful ways to collect stem cells and better transplant outcomes. There is a large, ongoing international market for this type of drug and likelihood of significant financial benefit.
Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal c ....Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal cellular differentiation is crucial. The studies outlined here aim to contribute to the understanding of the these processes and hence help to provide the framework for future studies aimed at more directly altering cell fate decision for clinical applications. Read moreRead less
A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at ....A novel role for the proteins Scribble & Dlg in the formation of cell protrusions and their effects on cell function. Dlg and Scribble are recently discovered proteins that are required during development, immune regulation, neural signalling and tumour suppression. Understanding how they work will enable the development of diagnostic and therapeutic tools that have the potential to influence an enormous range of diseases, from cancer to immunodeficiencies and autoimmune diseases. Researchers at the PeterMac perform world-leading research into the biology of Scribble and Dlg, and their role in cancer biology and immune function. The mechanistic insight provided by this project will continue that tradition, and facilitate translation of our basic research into clinical applications in important disease areas.Read moreRead less
CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opport ....CD151 and functional overlap in tetraspanins. The applicants are currently world leaders in the tetraspanin field. This project will enhance existing international collaborations to maintain and increase the applicants', and hence Australia's, international standing in this field and Australia's reputation in cell and molecular biology in general.
The project will greatly increase our understanding of this important but poorly understood family of proteins. It will also provide training opportunities for postgraduate students in state-of-the-art approaches in biotechnology.Read moreRead less
Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently ....Development of a prime-boost anti-cancer vaccine. New vaccination strategies are urgently needed for a variety of diseases, including cancer. The problem with cancer vaccines is that it is difficult to trigger a response to a self protein. We propose that a prime-boost vaccination, using yellow fever virus and modified vaccinia virus ankara, could create very strong responses against tumor antigens. This approach can be patented and can revive that field of tumor vaccination, which is currently restrained by the difficulty of breaking immunological tolerance. We envisage the construction of a anti-cancer vaccine vector with obvious market potential. An exciting prospect is that this approach could be used as a prophylactic vaccine and possibly also as a therapeutic vaccine.Read moreRead less
Regulation of tissue morphogenesis in reproductive function and metastatic cancer. Infertility, endocrine and metabolic disorders and reproductive cancers are all increasing medical problems and principal contributors to morbidity and mortality in the Australian community. This research takes the novel approach of investigating the mechanisms of dynamic remodeling in reproductive organs. Novel hormonally controlled mechanisms of tissue remodeling unique to reproductive organs and cancers in ad ....Regulation of tissue morphogenesis in reproductive function and metastatic cancer. Infertility, endocrine and metabolic disorders and reproductive cancers are all increasing medical problems and principal contributors to morbidity and mortality in the Australian community. This research takes the novel approach of investigating the mechanisms of dynamic remodeling in reproductive organs. Novel hormonally controlled mechanisms of tissue remodeling unique to reproductive organs and cancers in adults have been discovered. The results are being applied to new medical alternatives for infertile patients and new diagnostics and therapeutics for patients with metastatic cancers. The information is also being applied to improve reproductive efficiency in animal production industries.Read moreRead less
A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell fr ....A New Model for 3D Migration Involving Claw Structures and Metalloproteinases. This proposal will revolutionize ideas related to cell movement through three-dimensional (3D) matrix. Our method in mimicking the body's dense 3D matrix environment have led to the discovery of a new cell structure called Claws, and the formulation of a new model for 3D invasion in high density matrix. We will study the genes that control this type of migration including those involved in the formation of the cell front (Claw region), the back of the cells and matrix digestion. This work will have significant impact on normal and pathological human conditions from immune responses to tissue regeneration and cancer.Read moreRead less
Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both with ....Identifying the pathways employed by growth hormone to regulate the proliferation of adult neural stem cells. As stem cells underpin the maintenance and regeneration of the brain and are known to decline in number and competence with age; understanding exactly how these cells are regulated is of broad national benefit. Furthermore, given the regulatory role of growth hormone throughout the body, insights gained from this project should lead to the discovery of novel therapeutic targets both within and outside the nervous system, ultimately leading to preventative and restorative strategies for maintaining good health. Finally, this Proposal is of significant national benefit as it will undoubtedly advance our knowledge base in stem cell biology, helping to maintain Australia as a global leader in stem cell research.Read moreRead less