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.
Determining The Mechanisms Underlying Chronic Visceral Pain And Providing Novel Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Gastroenteritis activates special types of nerve endings in the gut to cause acute pain. In chronic gut pain, although the damaged tissue has healed, the nerve endings remain active and don’t reset back to normal. This project will identify why this occurs, determining pain mechanisms associated with Irritable Bowel Syndrome, a leading form of chronic pain. It will identify which ion channels and receptors can be targeted allowing the development of novel and effective therapies for pain relief.
Trafficking Mechanisms Governing Receptor Availability For Signalling
Funder
National Health and Medical Research Council
Funding Amount
$526,978.00
Summary
Receptors on the cell surface allow cells to respond to their environment. We have recently discovered a new pathway for controlling the amount of receptors displayed on the cell surface, errors within which will lead to defects in development and diseases like cancer. We are studying how this new pathway controls the balance between how much receptors are destroyed after being activated and how much are recycled back for re-use.
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of ele ....Regulatory mechanisms for calcium release-activated calcium channels. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, growth factors and other physiological stimuli. The aims of this project are to elucidate the mechanisms that regulate the activity of store-operated channels and how their properties can be modulated by different pharmacological agents. Using chiefly the techniques of electrophysiology and molecular biology we expect to learn the fundamental mechanisms that modulate the opening and closing of store-operated calcium channels and to gain an important information that can be used for determining the molecular structure of these channelsRead moreRead less
The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progress ....The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progression. The work will contribute to the training of one or more graduate students in a technologically advancing and internationally competitive field.Read moreRead less
Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential ....Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential-1 (TRP-1) protein in hepatocytes. The electrophysiological properties, mechanisms of activation and intracellular trafficking of the channels will be investigated. It is anticipated the results will provide basic information on the physiological functions of second messenger-activated calcium channels. This will benefit the understanding of liver function, hepatotoxicity in animals, animal production and the development of pharmaceuticals in animal husbandary.Read moreRead less
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
Dissecting The Pseudoexfoliation Syndrome With Complementary Genetic, Proteomic And Biophysical Strategies
Funder
National Health and Medical Research Council
Funding Amount
$490,352.00
Summary
Pseudoexfoliation syndrome (PEX) is an eye condition in which flaky material deposits in the eye, greatly increasing the risk of cataract and glaucoma which can lead to blindness. PEX is also associated with heart disease, strokes and aneurysms. Cataract surgery in PEX patients has a higher rate of complications. In this project we will determine the nature of PEX material and why it forms. This knowlege will facilitate better diagnosis and treatment of PEX preventing associated blindness.
Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less