The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. The aim of the project is to determine how these white blood cells accumulate in the glomerulus, specifically asking the question, what molecules present on the white blood cells and the glomerular blood vessels are required for this accumulation?
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
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
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100170
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Bioaffinity mass spectrometry infrastructure to identify small molecules binding to therapeutic targets. The development of anti-infective therapies is challenging because the underlying biology and biochemistry of pathogen virulence is not yet completely understood. This mass spectrometer facility will be used to identify small molecules suited for development into new therapies for malaria, tuberculosis and HIV.
Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). GPCRs are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
New methodology for the manufacture of opioid pharmaceuticals and the discovery of novel opiate receptor ligands. Semi-synthetic opiates are important analgesic agents and are used in the treatment of alcohol and opiate dependence. This project will focus on the application of new, greener and more efficient methods for the preparation of these medicinal agents.