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
Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation a ....Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation and manipulation of these stem cell types to benefit the community. The work will also provide postgraduate students with training in state of the art genomic techniques and in the interface between bioinformatics and experimental science. 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.
Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell sign ....Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell signal transduction that drive cell division, differentiation and transformation and may enable the design of new anticancer therapies. Importantly, the modelling and simulation methods developed in the project will have a general applicability to other complex systems such as sustainable ecological systems.Read moreRead less
Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new ....Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new therapeutics, diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less
Bioreactors for manufacture of human platelets. Blood cell transfusion is a critical part of medicine that is supported by volunteer donors. Unfortunately, the demand for blood cells for transfusion far outstrips supply and therefore new strategies are required for manufacture of blood cells. This project will lead to the development of technology for manufacture of human platelets from stem cells. The systems devised will be applicable to a broad range of other blood cell types.
Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well ....Control of cell survival by the Bcl-2 protein family. The control of apoptosis is essential for homeostasis. It is now realized that deregulation of apoptosis is a hallmark of many cancers. In apoptosis, the Bcl-2 protein family plays a central role in determining if a cell lives or dies. My proposal aim is to provide a deeper understanding of how cell death and survival is controlled by the Bcl-2 family. These studies have notable implications for understanding normal cell death control as well as aid in the development of therapeutic agents such as ones to overcome the resistance to apoptosis, found in many types of cancer.Read moreRead less
Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally inf ....Apoptotic signalling in virally infected and normal cells. Viral diseases contribute substantially to mortality and morbidity, in Australia and internationally. Emerging viral diseases, including H5N1 avian influenza, have the potential to severely impact on human health and the global economy. Concerns also exist that viruses may be used as bioweapons. This project seeks to define the mechanisms by which cell death occurs and is regulated in healthy cells, and how this is altered in virally infected or oncogenically transformed cells. Outcomes of this work may contribute to development of novel anti-cancer and anti-viral therapies, diagnostic reagents and vaccines.Read moreRead less
Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more ef ....Mechanisms of cell death regulation by the Bcl-2 protein family. Through the proposed study, the expected outcome is a better understanding of the important process of how the Bcl-2 family of proteins interact with each to control cell death. Furthermore, as dysfunctional apoptosis signalling contributes to diseases such as autoimmune conditions, neurodegenerative disorders and cancer, a detailed and sound understanding of how the cell death machinery operates should enable the design of more effective and importantly, safer therapies against these pathologies.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