A Structural Understanding Of Class B G Protein-coupled Receptor Function
Funder
National Health and Medical Research Council
Funding Amount
$1,289,570.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins that enable communication from external signals to the inside of cells of the body. Class B GPCRs are a therapeutically important subclass of these receptors and they play crucial roles in bone and energy homeostasis, cardiovascular control and immune response. This grant will uncover fundamental knowledge on how these receptors work, and will enhance future development of therapeutics.
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.
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.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
Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells i ....Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells in real-time with high sensitivity. This project could have broad benefits for and affect study of all aspects of the life sciences at the cellular and molecular levels. How these protein complexes function in cells underpins much of our understanding of biology, and technological tools.Read moreRead less
Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their ....Beyond structure - solving conformational dynamics for intractable proteins. Proteins perform almost every task that enables the amazing complexity of cellular and whole organism physiology. These molecular machines perform this incredible array of tasks due to their ability to dynamically change shape. For the vast majority of these machines, we can only view a snapshot of the possible shapes they can adopt and can’t monitor how they change from one shape to another, which is critical for their functioning. This project aims to develop and apply a completely new method to visualise dynamic changes in protein shape which is not possible with current techniques. This will allow us to provide a new description and understanding of the function of proteins, which is fundamental to all biology.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
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
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