LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
Capturing New Drugs That Selectively Modulate PAR2 Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$469,088.00
Summary
Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory ....Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory diseases, diet-induced obesity and cancers.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100164
Funder
Australian Research Council
Funding Amount
$310,000.00
Summary
A facility for ex-vivo molecular imaging. The facility will allow a consortium of Australian researchers to create an integrated facility for imaging biological receptors in tissue, bringing together laboratory, radiochemistry and imaging expertise. Digital data at each site will be able to be viewed and analysed remotely.
Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learne ....Allosteric and Bitopic Ligands Acting at G Protein-Coupled Receptors. This project seeks to gain a more detailed understanding of the mechanisms of the function of G protein-coupled receptors (GPCRs) using novel chemical tools. GPCRs are the largest group of cell surface signalling proteins and are responsible for the regulation of numerous vital physiological functions. They are the target of over 30 per cent of currently used pharmaceuticals. Despite their importance, much remains to be learned about the regulation of GPCRs by small molecules. This project aims to address this gap by focusing on novel regions on these proteins, termed allosteric sites, to explore novel modes of GPCR regulation which may offer the potential of identifying pathway selective agents.Read moreRead less
Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radi ....Pharmacological probes to facilitate preclinical development of modulators of a6 subunit containing nicotinic acetylcholine receptors. Allosteric modulators of alpha7 nicotinic acetylcholine receptors have a promising future as drugs targeting attention deficits in Alzheimer’s disease and schizophrenia but the mechanisms underlying modulation are poorly understood. This project aims to determine its binding site and develop a radioactive labelled compound that competes with its binding. The radiolabelled compound and a deeper insight into the mode of action will enable development of ligands for positron emission tomography (PET) which will aid in the development of BNC375 as well as other alpha7 modulators.Read moreRead less
Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-t ....Toxins from Down Under: Novel tools to understand and modulate ion channels. Venoms are complex secretions containing biologically active components that have evolved over millions of years to specifically target the nervous systems of predators and prey. Two novel classes of toxins from snake and plant venoms that act on voltage-gated sodium channels, key proteins that regulate neuronal excitability, were recently identified by the research team. The project aims to develop and apply state-of-the-art chemical, structural and biological techniques to unravel the molecular mechanisms through which these novel toxin classes act at their targets. Insights gained from this project will help identify and develop novel channel-modulating molecules that may have applications as neuroscience tools, diagnostics or drugs.Read moreRead less
The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement ....The potential of membranes – peptide engineering to modulate ion channels. This project aims to develop a platform technology to identify new and selective sodium channel inhibitors based on ultra-stable venom peptides that can interact with and cross membranes. Sodium channels are involved in almost all aspects of human physiology. The ability to selectively inhibit individual sodium channel subtypes and to understand what drives peptides' ability to cross membranes would be a major achievement and lead to new neuroscience research tools and technologies. This project’s proposed technology could be translated into new knowledge relevant to the biotechnology industry.Read moreRead less
Stabilising biased allosteric G protein-coupled receptor conformations. This project aims to develop and identify molecules that can stabilise distinct calcium sensing receptor (CaSR) conformations. The CaSR is a G protein-coupled receptor (GPCR) vertebrates need to live. GPCRs are responsible for virtually all (patho)physiological processes. They are structurally very flexible, but this has hindered their structural determination. Developing and validating the proposed molecules should help fut ....Stabilising biased allosteric G protein-coupled receptor conformations. This project aims to develop and identify molecules that can stabilise distinct calcium sensing receptor (CaSR) conformations. The CaSR is a G protein-coupled receptor (GPCR) vertebrates need to live. GPCRs are responsible for virtually all (patho)physiological processes. They are structurally very flexible, but this has hindered their structural determination. Developing and validating the proposed molecules should help future structural studies of an important GPCR. The project expects to enhance understanding of the structure and function of the CaSR and ultimately of the GPCR superfamily, which will ultimately lead to opportunities to discover new drugs.Read moreRead less
An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membr ....An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membrane biology, and by leveraging global scientific inputs through online research methods allowing anyone to participate.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