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
Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to ....Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to discover the specificity of PAT-SM6 for proteins and protein complexes and how these interactions lead to tumour cell death. This work will enhance the effectiveness of human antibody therapies and help in the development of this fast growing area within the biotechnology industry in Australia.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
Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.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
THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providi ....THE ROLE OF SMALL NON CODING RNAS IN BONE MARROW MEDIATED TUMOR ANGIOGENESIS. Despite advances in treatment and diagnosis cancer remains the leading underlying cause of deaths, representing about a third of all deaths each year in Australia (ABS stats. www.abs.gov.au). The ability to understand the process of tumour vascularisation and spread has enormous economic and social outcomes. Indeed, the most effective anti-angiogenic therapy developed to date Avastin (aka Bevacizumab), although providing only a modest survival advantage (4-6 months) has annual sales of several billion dollars. microRNA represent a relatively newly discovered form of gene activity regulation. Taking a key leadership role in this area will put Australian science at the forefront of international research initiatives.Read moreRead less