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
Therapeutic Implications Of A Molecular Link Between Survivin And Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
A unifying feature of all types of cancer cells is that they are immortal. Our investigations will build upon our recent results that showed the gene survivin is involved in cancer cell immortalisation. We will characterise a molecular link between survivin and the enzyme telomerase, which is central to cancer cell immortality. Furthermore, we will demonstrate the therapeutic potential of turning off both survivin and telomerase as a novel approach to halting the growth of cancer cells.
Through this Australia Fellowship, Prof Keall and his tream will substantially improve the accuracy and effectiveness of radiation therapy for cancer by developing new techniques that will be able to ‘target’ a tumour in real-time and ‘concentrate fire’ on the most resistant and aggressive parts of it. Success in physiological targeting will create a paradigm shift in radiation therapy and could literally be a lifesaver. It’s a big challenge, but if this five-year research program succeeds, it w ....Through this Australia Fellowship, Prof Keall and his tream will substantially improve the accuracy and effectiveness of radiation therapy for cancer by developing new techniques that will be able to ‘target’ a tumour in real-time and ‘concentrate fire’ on the most resistant and aggressive parts of it. Success in physiological targeting will create a paradigm shift in radiation therapy and could literally be a lifesaver. It’s a big challenge, but if this five-year research program succeeds, it will pay big dividendsRead moreRead less
Benthic Processes and Oceanic Internal Waves. Direct observations will be made of the turbulent motion and sediment re-suspension near the sea bed of the ocean in regions strongly influenced by tides and internal waves. Combined with numerical models, the study will provide new insights into processes that are of fundamental importance to understanding the global dissipation of tidal energy and the role of internal waves in these processes. With observations from the continental slope region of ....Benthic Processes and Oceanic Internal Waves. Direct observations will be made of the turbulent motion and sediment re-suspension near the sea bed of the ocean in regions strongly influenced by tides and internal waves. Combined with numerical models, the study will provide new insights into processes that are of fundamental importance to understanding the global dissipation of tidal energy and the role of internal waves in these processes. With observations from the continental slope region of the Australian North West Shelf, results will also benefit the offshore engineering industry through knowledge of sediment scour and loadings on offshore structures.Read moreRead less
Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.
Discovery Early Career Researcher Award - Grant ID: DE130101591
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Novel postsynaptic functions of the microtubule-associated protein tau. The protein tau is present in abnormal deposits in brains of individuals with dementia. The main aim of this project is to unravel and understand in detail new roles of tau in neurons and thus shed new light into normal brain function. Understanding these new functions of tau will aid in identifying new ways to treat these debilitating diseases.
Cellular mechanisms that protect against copper-bound beta-amyloid. This project will investigate some of the brain’s own mechanisms for protecting itself against Alzheimer’s disease. Understanding these mechanisms will be important for developing future therapeutic strategies for treating Alzheimer’s disease.
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less