Using Protein Structure And Dynamics To Facilitate Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$1,512,250.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human genome, and drugs targeting these receptors account for 35% of marketed drugs. This project aims to determine atomic-level structural information of how drugs bind and specifically interact with therapeutically relevant GPCRs. Outcomes of this research will facilitate the design of future development of selective and effective drugs.
Restoring Neuroprotective Sphingosine 1-phosphate Signalling In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,656.00
Summary
Our research team has recently shown that a vital signalling lipid called S1P is lost from the brains of people who are in the early stages of developing Alzheimer's Disease. S1P protects brain cells against toxic insults that cause Alzheimer's Disease. This project will investigate how loss of S1P sensitizes people to the development of Alzheimer’s Disease, and the effectiveness of clinical drugs that restore S1P signals in protecting against Alzheimer’s Disease and restoring brain function.
It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of ....It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of depression. If true, this could have important practical implications for preventative mental health, in identifying those at greatest risk if depression and counselling them to avoid stressful situations. However, success in replicating this finding has been mixed, and this is possibly because another important risk factor, social support, has not been taken into account. We have DNA samples from over 5000 twins who have been assessed for depression and risk factors including SLE and SS. This will give us unprecedented power to estimate the importance of the genotype x environment interaction. We shall also type other genes that have been implicated in depression and check for interactions with life events and social support. Our results will inform preventative strategies in mental health practice.Read moreRead less
Molecular Determinants Of Drug Binding And Selectivity At Muscarinic Acetylcholine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$816,866.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in the human genome, and drugs targeting these receptors account for 30% of marketed drugs. This project aims to determine high resolution structural information on how drugs bind and specifically interact with GPCRs, which will enable future development of selective and effective drugs.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.
The Structural Basis Of Ligand-Induced Activation Of The Insulin Receptor
Funder
National Health and Medical Research Council
Funding Amount
$640,825.00
Summary
We aim to understand how insulin binds to and activates its cell-surface receptor. This information has implications for the design of anti-diabetic agents targetted directly to the insulin receptor. Diabetes is a global health problem and is classified by the World Health Organization as an epidemic. The results also have implications for the insulin-like growth factor receptor system and the design of anti-cancer therapeutics directed towards it .