Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex ....Differential Isotope Proteome Mapping of Transforming Growth Factor Beta Cell Signalling. Our research will capitalise on Australia's expertise and prior infrastructure investments in frontier, proteomic technologies to elucidate novel intracellular signalling pathways that contribute to the development of cancer. New approaches will be developed using isotopes to provide sensitive and accurate measurements of changes in protein expression levels. This technology will allow us to define complex intracellular signalling networks. This is an important step towards identifying new drug targets that are responsible for tumour growth. Australian science will benefit from the training of new scientists in modern, post-genome technologies where there is currently a world shortage of experienced personnel.Read moreRead less
Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that tr ....Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that translate external signals into the right cellular responses. The proposed experiments will provide a unique structural framework by which we can understand how these signals are transmitted. Such knowledge is an important foundation for advances in biomedical research and biotechnology applications.Read moreRead less
Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcom ....Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcome the challenges of flexibility in these systems. The proteins we will study are not found in humans, and hence our research will provide important structural data on potential targets for the design of novel antibiotics to fight bacterial infection.Read moreRead less
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living s ....Understanding biological nitrogen fixation: an investigation of multi-electron reduction catalysis at novel iron-sulfur clusters. A new class of iron-sulfur clusters held together by a central light atom will be prepared and their reactions thoroughly studied. These clusters are important because they will have the same structure as the iron-molybdenum cluster of the enzyme nitrogenase. This enzyme fixes atmospheric nitrogen as ammonia. It is the primary route of nitrogen entry into all living systems. Industrially ammonia is produced in an energy-demanding process on a vast scale. The studies will provide insights into how nitrogenase works and how to design new multi-electron reduction catalysts. The research may lead to new energy-efficient routes to ammonia and to other new alternative fuel sources. Such processes would transform Australian industry and how we live.Read moreRead less
DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that in ....DNA Nanoshuttles: A New Class of DNA-Binding Molecules. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. DNA-nanoshuttles are ring-shaped molecules that thread onto DNA and shuttle from one end to the other. This threading interaction is without precedent and hence DNA-nanoshuttles have significant potential applications in all areas of medicine, biotechnology and nanotechnology that involve DNA interactions. This research may lead to the design of new 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