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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.
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechani ....Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechanisms by which the Ctr proteins transport copper across eukaryotic cell membranes, by solving their three-dimensional structures by X-ray crystallography.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100066
Funder
Australian Research Council
Funding Amount
$443,311.00
Summary
Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided ....Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided by the high-throughput, automated patch clamp system is that it allows up to 384 cells to be recorded simultaneously. This project expects to enhance capacity to automate and standardise the quality of recordings, substantially increase the rate of data production, and enable greater access to patch clamp technology.Read moreRead less
How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump acti ....How cholesterol optimises ion pump function in animal membranes. This project aims to determine how cholesterol optimises ion pump function in animal membranes and to identify the major effects of cholesterol and its derivatives on membranes’ physical properties. All animal cells need high levels of cholesterol in the plasma membrane for survival. Insufficient cholesterol biosynthesis leads to severe birth defects. The need for cholesterol is likely linked to its acceleration of sodium pump activity, essential to physiological processes including cell division, nerve, muscle and kidney activity. An expected benefit of the project is knowledge on the molecular origin of diseases associated with inhibition of cholesterol production, and a more complete understanding of the crucial role played by cholesterol via its effect on ion pumping towards the healthy functioning of vital organs, particularly in heart muscle and nerves.Read moreRead less
Nicotinic receptor structure and function probed with conotoxins. Nicotinic receptors are intrinsic membrane proteins that play a role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are to define the structural and functional determinants of nicotinic-conotoxin interactions at a molecular level, and develop new selective probes that advance neurophysiological research. The diversity and distribution of nicotinic receptor subtypes being ....Nicotinic receptor structure and function probed with conotoxins. Nicotinic receptors are intrinsic membrane proteins that play a role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are to define the structural and functional determinants of nicotinic-conotoxin interactions at a molecular level, and develop new selective probes that advance neurophysiological research. The diversity and distribution of nicotinic receptor subtypes being uncovered through molecular biology and selective conotoxin probes presents an exciting opportunity for the discovery of new therapeutic agents.Read moreRead less