Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are ....Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are targets for anaesthetics and drugs of abuse. GlyRs are also important in modulating pain sensation by the brain. New insights into how natural agonists and drugs affect ion channel structure and function may lead to novel therapeutic opportunities and improved drug structure predictions.Read moreRead less
Membrane proteins in innate immunity. The application of smarter and faster methods for understanding membrane proteins, targets of most drugs, is vital to a knowledge-based economy and a healthy society. The long-term benefits will include fundamental new knowledge on immunity, and implementation of new approaches that streamline costs and efforts of challenging, high-impact research.
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Unravelling the structural complexity of ancient Australian arthropod venoms. Animal venoms contain a complex mix of molecules that have evolved over millions of years to target various biological processes. Their exquisite specificity and potent activity has made them an attractive source for development as therapeutic drugs with fewer side effects or as environmentally friendly insecticides. This project aims to for the first time explore the three-dimensional structure of all known classes of ....Unravelling the structural complexity of ancient Australian arthropod venoms. Animal venoms contain a complex mix of molecules that have evolved over millions of years to target various biological processes. Their exquisite specificity and potent activity has made them an attractive source for development as therapeutic drugs with fewer side effects or as environmentally friendly insecticides. This project aims to for the first time explore the three-dimensional structure of all known classes of toxins in the venom of two ancient Australian arthropods (spiders and centipedes). This will provide a comprehensive overview of these venoms and provide opportunities in engineering new classes of venom based drugs and insecticides. Read moreRead less
A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevale ....A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevalent in immune responses, and all recognise pMHCI using a conserved orientation. This project aims to use this observation to study the relationship between TCR recognition modes and T cell recruitment and activation.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Molecular Resolution 3D Atlas of the Photosynthetic Machinery. The project aims to produce an atomic-resolution 3-D atlas of the photosynthetic machinery of single-cell green algae to guide the targeted engineering of high efficiency algae production cell lines and bio-inspired artificial solar fuel systems. Photosynthesis drives the first step of all algae production processes by capturing solar energy and converting it to chemical energy (for example sustainable fuels, food and high value prod ....Molecular Resolution 3D Atlas of the Photosynthetic Machinery. The project aims to produce an atomic-resolution 3-D atlas of the photosynthetic machinery of single-cell green algae to guide the targeted engineering of high efficiency algae production cell lines and bio-inspired artificial solar fuel systems. Photosynthesis drives the first step of all algae production processes by capturing solar energy and converting it to chemical energy (for example sustainable fuels, food and high value products), but excess light can cause photodamage. Microalgae have evolved intricate photo-protection mechanisms that can dissipate up to 90 per cent of the captured light energy. Fine-tuning the light harvesting complexes could considerably increase efficiency.Read moreRead less
Membrane proteins: understanding biological switches, motors and triggers. By extending the range of biomolecular systems that can be modelled computationally at the atomic level, this project will enable fundamental cellular processes such as how molecules are transported across cell membranes or how the binding of a hormone to an extracellular receptor sends a signal in a cell to be understood in unprecedented detail.
Understanding biological membranes in atomic detail. The aim of the project is to develop the capacity to represent specific mammalian, fungal and bacterial membranes in atomic detail and to use such models to understand the role of membrane composition in the structure and dynamics of membrane proteins at an atomic level. Membrane protein assemblies are the ultimate nanoscale machines. Understanding these sub-cellular components is both a fundamental theoretical challenge and of widespread prac ....Understanding biological membranes in atomic detail. The aim of the project is to develop the capacity to represent specific mammalian, fungal and bacterial membranes in atomic detail and to use such models to understand the role of membrane composition in the structure and dynamics of membrane proteins at an atomic level. Membrane protein assemblies are the ultimate nanoscale machines. Understanding these sub-cellular components is both a fundamental theoretical challenge and of widespread practical importance in biochemistry, structural biology and medicine. By representing in detail the complexity of biological membranes, the project aims to elucidate the role played by specific membrane components in determining the mechanism of action of proteins involved in transport and signal transduction in context.Read moreRead less
Mechanism of AMPK activation by drugs and metabolites. This project aims to identify the molecular basis of activation mechanisms in the AMP-activated protein kinase (AMPK), an enzyme that regulates burning and storage of fuels such as fat and sugars, autophagy and controls appetite and energy expenditure. This project expects to provide insights into how energy metabolism and physiological functions are linked.