Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulat ....Constructing an embryo. This project investigates the cellular and molecular mechanisms underlying temporal and spatial organisation in the eutherian preimplantation embryo. It will examine: the relative roles of cell cycle and circadian clocks in developmental timing; the molecular mechanism by which intercellular adhesion patterns influence spatial organisation; the extent to which marsupials use similar timing and spatial localisation mechanisms to eutherians; the impact of in-vitro manipulations over the first 5 days of mouse pregnancy on embryonic temporal and spatial organisation.Read moreRead less
Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when th ....Molecular control of apoptosis and protein homeostasis. A million cells are produced every second by cell division. At the same time a million cells commit suicide by a process called apoptosis. When cells fail to die when they should they can develop into cancers. In heart attacks, stroke and neurodegenerative diseases, many cells appear to activate their self destruct mechanism to die unnecessarily. Drugs that can cause cancer cells to kill themselves, or drugs that prevent cells dying when they shouldn't, would make a major impact on many important diseases. Understanding the molecular mechanisms of cell death is the first step towards developing these drugs.Read moreRead less
New Methods for Structural Biology in Solution. It is proposed to establish a new research group that focuses on the development of new nuclear magnetic resonance (NMR) technologies and applications to problems concerning protein structure and function. This includes
- the exploitation of new NMR parameters;
- optimization of an inexpensive in vitro protein expression system;
- development of experimental strategies for the identification of protein-ligand surfaces by chemical modificatio ....New Methods for Structural Biology in Solution. It is proposed to establish a new research group that focuses on the development of new nuclear magnetic resonance (NMR) technologies and applications to problems concerning protein structure and function. This includes
- the exploitation of new NMR parameters;
- optimization of an inexpensive in vitro protein expression system;
- development of experimental strategies for the identification of protein-ligand surfaces by chemical modification, as a basis for high-throughput mass spectrometrical analyses;
- development of an algorithm for rapid resonance assignment of 15N-labelled proteins which is of importance for the pharmaceutical industry;
- 3D structure determinations of proteins and protein domains.Read moreRead less
Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of b ....Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of bacteria were amongst the first organisms trialed as biological weapons, and the pathogenic species remain rated as Class 3 organisms by the Centers for Disease Control.Read moreRead less
The diversity and assembly of optics in nature. Optics, such as the design of new coloured reflectors, is a research strength for Australia. A reason for this is the potential for application - optical devices can be found far and wide in our everyday lives, from security devices on banknotes (holograms), to computer monitors (LCDs). An interesting parallel exists in nature - animals possess similar optical devices to those we use. So it makes sense to examine the animals' devices in a search fo ....The diversity and assembly of optics in nature. Optics, such as the design of new coloured reflectors, is a research strength for Australia. A reason for this is the potential for application - optical devices can be found far and wide in our everyday lives, from security devices on banknotes (holograms), to computer monitors (LCDs). An interesting parallel exists in nature - animals possess similar optical devices to those we use. So it makes sense to examine the animals' devices in a search for new reflectors, and that's an aim of this project. And since reflectors are often difficult to make, why not let animals make reflectors for us? That is a further aim of this project. Soon we may have genetically-altered butterfly scales embedded in our credit cards that cannot be counterfeited.Read moreRead less
Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive unders ....How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive understanding of the AMP activated protein kinase (enzyme isoforms, genes, physiological roles and regulation). This knowledge will have major benefits in biopharmaceutical development, the livestock, plant and sport/racing industries.Read moreRead less
An investigation into Infection, Immunity & Rational Drug Design. The human population is constantly under threat of microbial attack. The survival of our species reflects a delicate balance between infection and immunity. Whether an individual mounts an effective immune response or succumbs to microbial infection is critically dependent on host proteins interacting effectively with microbial antigens, versus microbes developing sophisticated strategies of invasion and immune evasion. This pr ....An investigation into Infection, Immunity & Rational Drug Design. The human population is constantly under threat of microbial attack. The survival of our species reflects a delicate balance between infection and immunity. Whether an individual mounts an effective immune response or succumbs to microbial infection is critically dependent on host proteins interacting effectively with microbial antigens, versus microbes developing sophisticated strategies of invasion and immune evasion. This proposal will provide fundamental advancement of knowledge in the areas of infection and immunity. The information gleaned from this research will lead to the rational development of therapeutics. Consequently, the research will potentially have an enormous global impact in the area of biomedical health.Read moreRead less