Understanding the role of methionine oxidation in amyloid formation. Amyloid deposition is associated with many debilitating systemic and neurological diseases, including Alzheimer's disease. This project aims to understand the effect of protein oxidation on the process of amyloid fibril formation. This knowledge will assist in the discovery of the triggers of these disorders and may identify methods of combating them.
Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This p ....Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This project aims to determine the basis of ion permeation and selectivity in the channels and explain the mechanisms of action for a number of common drugs. This will provide a foundation for future drug development to target specific channels for improved treatment of epilepsy, chronic pain and arrythmias. Read moreRead less
Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which fu ....Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Building on recent breakthroughs made at St. Vincent's Institute, this project will produce innovative research into novel mechanisms that control AMPK. These discoveries will greatly increase our understanding of AMPK regulation by cellular processes, and aid the design of more effective AMPK drugs.Read moreRead less
Structural basis of gating in hERG potassium ion channel proteins. This project aims to use cryo-electron microscopy to determine atomic resolution structures of open, closed and inactivated states of an ion channel important for regulating activity in the heart and the brain. This work will provide fundamental insights into how ion channel proteins utilise electrochemical energy to mechanically open and close gates that regulate ion flow across cell membranes. Electrical signalling is ubiquitou ....Structural basis of gating in hERG potassium ion channel proteins. This project aims to use cryo-electron microscopy to determine atomic resolution structures of open, closed and inactivated states of an ion channel important for regulating activity in the heart and the brain. This work will provide fundamental insights into how ion channel proteins utilise electrochemical energy to mechanically open and close gates that regulate ion flow across cell membranes. Electrical signalling is ubiquitous in biology but is of particular importance in the brain and heart where ion channels are important therapeutic targets for cardiovascular and psychiatric diseases. Read moreRead less
Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which fu ....Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Building on recent breakthroughs made at St. Vincent's Institute, this project will produce innovative research into novel mechanisms that control AMPK. These discoveries will greatly increase our understanding of AMPK regulation by cellular processes, and aid the design of more effective AMPK drugs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: De180101165
Funder
Australian Research Council
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.