GABA(B) Receptor Modulation Of Gastrointestinal Function In Health And Disease By Alpha-Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
Chronic visceral pain is a common and debilitating condition arising from numerous diseases that affect our internal organs. There is a desperate need for more information about the mechanisms responsible for signalling chronic visceral pain to provide therapies and potentially find a cure for it. Our research focuses on ?-conotoxins (small peptides from marine cone snail venom) as novel potential therapeutic agents for the treatment of chronic visceral pain.
Molecular Mechanisms Of Receptor Activation And Signalling
Funder
National Health and Medical Research Council
Funding Amount
$571,980.00
Summary
Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several ....Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.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.
Discovery Early Career Researcher Award - Grant ID: DE120102645
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The cause of the poleward shift of Earth's storm tracks and jet streams. Why do global climate models shift the atmospheric storm tracks and jet streams poleward in simulations of future climate? This project will determine the underlying causes of the most important circulation change that is projected to occur with increasing greenhouse gases, and will allow much more accurate regional climate projections.
Transforming our research capacity in the analysis of climate extremes. Given their devastating impacts, there is now a critical urgency to understand what drives extreme climate events and make timely predictions of their future risk. The analysis of comprehensive extremes datasets, comprising global observations and output of multi-model simulations, will greatly improve our ability to answer fundamental questions about the nature and variability of extreme climatic events. This project also e ....Transforming our research capacity in the analysis of climate extremes. Given their devastating impacts, there is now a critical urgency to understand what drives extreme climate events and make timely predictions of their future risk. The analysis of comprehensive extremes datasets, comprising global observations and output of multi-model simulations, will greatly improve our ability to answer fundamental questions about the nature and variability of extreme climatic events. This project also ensures the government's continued commitment to managing the risks associated with extreme events as an urgent national priority. It represents a landmark opportunity for Australian leadership of an international collaboration between some of the world's leading climate scientists and climate data and modelling centres.Read moreRead less
Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
Cloud-climate interaction over the Great Barrier Reef and Southwest Pacific. This project aims to investigate cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The project expects to generate new knowledge in the nature and variability of the trade wind clouds, including their impact on the surface radiative budget, ocean temperatures and coral bleaching events. Potential changes of these clouds due to glob ....Cloud-climate interaction over the Great Barrier Reef and Southwest Pacific. This project aims to investigate cloud-climate interactions of the Southwest Pacific trade wind region from the regional scale to local forcing over the Great Barrier Reef. The project expects to generate new knowledge in the nature and variability of the trade wind clouds, including their impact on the surface radiative budget, ocean temperatures and coral bleaching events. Potential changes of these clouds due to global warming and ensuing impacts on the environment will be studied. Expected outcomes include better modelling of the Great Barrier Reef environment and improved estimates of low-cloud feedback. This should provide significant benefits in developing warning systems for bleaching events, and regional land and water management. Read moreRead less