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Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechani ....Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechanisms by which the Ctr proteins transport copper across eukaryotic cell membranes, by solving their three-dimensional structures by X-ray crystallography.Read moreRead less
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less
Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit ....Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit it for our own benefit is needed. This project aims to anticipate evolution by simulating it in the laboratory, allowing for the best preparation for change. New pesticides will be designed to combat insecticide resistance based upon the molecular structure of an insect CBE. This project aims to exploit these newly evolved enzymes to create biosensors and decontamination agents.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less
From energy stress to hormones: new signals in bacteria and plants. This project will use molecular tools to detect and identify new chemical signals, known as butenolides, that regulate the growth and development of bacteria and plants. This project will use innovative, interdisciplinary techniques to discover where these butenolide signals come from, and how both bacteria and plants detect them. Expected outcomes of this project include a greater understanding of how plants use butenolides to ....From energy stress to hormones: new signals in bacteria and plants. This project will use molecular tools to detect and identify new chemical signals, known as butenolides, that regulate the growth and development of bacteria and plants. This project will use innovative, interdisciplinary techniques to discover where these butenolide signals come from, and how both bacteria and plants detect them. Expected outcomes of this project include a greater understanding of how plants use butenolides to cope with stress such as drought or salinity, and the design of new technologies for manipulating the growth of both plants and bacteria. The long-term benefits of this work should include fresh approaches for enhancing plant performance under sub-optimal conditions.Read moreRead less
Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-m ....Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-molecule biophysical techniques has begun to challenge many aspects of the elegant textbook view of replisome function. This approach is expected to reveal how synthesis of the two DNA strands in different directions at the same time is coupled together and how timing mechanisms work.Read moreRead less
A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA str ....A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA strands and how it exchanges protein components on the fly. Expected outcomes of this project include improved understanding of a fundamental biological process, development of novel biophysical methodology, and training of the next generation of interdisciplinary scientists.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