Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
The Pharmacology And Toxicity Of Synthetic Cannabinoids
Funder
National Health and Medical Research Council
Funding Amount
$744,808.00
Summary
Synthetic cannabinoids (SCs) have been recently linked to many deaths and hospitalizations but there is limited data available that addresses these issues. We have identified SCs which display unprecedented cannabinoid receptor function, unusual selectivity, and SCs with high activity at cannabinoid receptors. This project will define the role of CB receptors in the actions of SCs, and provide an evidence-based rationale for treating SC overdoses.
Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, ....Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, bias and heteromerisation. Expected outcomes also include generation of new pharmacological tools through interdisciplinary collaborative research between multiple institutions. There is significant expected economic benefit through commercialisation of new tools and facilitation of novel drug discovery.Read moreRead less
The Inhibition Of Biotin Protein Ligase As A New Source Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$750,167.00
Summary
We have become so accustomed to treating bacterial infections with antibiotics that it is hard to imagine life without them. However, the emergence of drug-resistance is creating a global health care crisis. Recently, there has not been enough attention paid to replacing old antibiotics with new products to combat drug resistance. Our team is addressing this challenge. We have discovered a new class of antibiotic that is unlike any other drug in clinical use.
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
Understanding How Toxins Interact With Lipid Membranes And Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
Chronic pain affects one in five Australians and current treatments have limited effectiveness, with only about one third of patients getting meaningful, pain relief. The aim of the current project is to create alternative treatments for pain that can potentially lead to the reduced suffering and improvement of life quality of many Australians. To achieve this aim we propose to study how spider toxins interact with cells and deactivate sensor targets responsible for chronic pain.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
Development Of A Novel And Highly Selective CDK4/6 Inhibitor For Treating Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,171,199.00
Summary
We have identified and patented novel drug molecules targeting enzymes namely CDKs 4 and 6, that are important for survival of cancer cells. The drugs are highly selective and potent against CDK4/6, well absorbed orally, and have attracted much interest from a pharmaceutical company. Further detailed work is needed to characterize fully their anti-cancer effects and toxicity, thereby securing a major investment from our commercial partner for drug development for treating cancers.
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
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.