Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Resolving the Structures of Human Muscarinic M1 and M4 Receptors. Muscarinic receptors are vital for most basic human brain functions. These receptors are changed in schizophrenia and Alzheimer's disease. This project will determine the structure and localisation of two of these receptors in order to i) understand their roles in brain disorders and ii) develop drugs to treat disorders involving them.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100206
Funder
Australian Research Council
Funding Amount
$550,000.00
Summary
Lattice light sheet microscopy for imaging biology in real space and time. This project aims to establish a Lattice Light-Sheet Microscope (LLSM) Facility, to provide the dedicated computing infrastructure needed for terabyte-scale image acquisition and handling. Lattice light sheet microscopy allows four-dimensional imaging of live biological specimens from individual molecules to small organisms. The microscope images live specimens without phototoxicity or photobleaching, enabling prolonged i ....Lattice light sheet microscopy for imaging biology in real space and time. This project aims to establish a Lattice Light-Sheet Microscope (LLSM) Facility, to provide the dedicated computing infrastructure needed for terabyte-scale image acquisition and handling. Lattice light sheet microscopy allows four-dimensional imaging of live biological specimens from individual molecules to small organisms. The microscope images live specimens without phototoxicity or photobleaching, enabling prolonged imaging of significant physiological or biophysical events. Expected outcomes include high impact discoveries and publications in fundamental research, rapid solutions for industry-focussed projects and opportunities for collaboration, research and development. The imaging is expected to reveal key scientific insights and showcase biology to the public.Read moreRead less
An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membr ....An Open Source Approach to Understanding an Important Parasite Ion Pump. This project plans to synthesise new compounds that bind the protein ATP4, an essential ion pump in the malaria parasite. It plans to generate a three-dimensional map to understand how these compounds stop ATP4 from working. Several promising new medicines for malaria target ATP4, yet we do not understand properly how they do so. The project’s intended aims will be achieved using new methods in synthetic chemistry and membrane biology, and by leveraging global scientific inputs through online research methods allowing anyone to participate.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101035
Funder
Australian Research Council
Funding Amount
$369,500.00
Summary
Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not under ....Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not understood. Recent work has identified a unique Apicomplexan sodium transporter and revealed a number of chloride transporter candidates. Using a combination of molecular biology and physiological techniques, this project aims to characterise the Apicomplexan sodium transporter in detail and elucidate the molecular mechanisms of chloride transport.Read moreRead less
Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its envi ....Regulating nutrient uptake in intracellular parasites. Parasites impose a major economic and medical burden on human societies. In order to grow and reproduce, parasites scavenge nutrients from their animal or human hosts. As they move within and between hosts they encounter different levels of nutrients; how they adapt to these differences is poorly understood. This project aims to investigate the mechanisms by which the model parasite Toxoplasma senses and responds to the nutrients in its environment, thereby shedding light on how they adapt to the different environments that they inhabit and, in the longer term, informing novel treatment strategies that aim to limit the parasites’ nutrient supply.Read moreRead less
The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter protein ....The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter proteins. The knowledge gained might help to combat Apicomplexan parasites by targeting these transporters’ native functions.Read moreRead less
Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologo ....Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologous proteins using biochemical, biophysical, and structural methods. It is expected that this project will provide fundamental insights into factors that dictate autotransporter folding and stability, which may enhance recombinant protein production and drive discovery of strategies to prevent autotransporter-mediated infection.Read moreRead less
Autotransporter assembly: new insights and biotechnological potential. The objective of this project is to improve our understanding of a fundamental biological problem: how autotransporters are assembled into cellular membranes. Autotransporters are a large family of bacterial proteins that play key roles in the pathogenesis of several infectious diseases. Currently, the precise mechanism by which disease-causing molecules are assembled into the outer membranes of bacteria and mitochondria is p ....Autotransporter assembly: new insights and biotechnological potential. The objective of this project is to improve our understanding of a fundamental biological problem: how autotransporters are assembled into cellular membranes. Autotransporters are a large family of bacterial proteins that play key roles in the pathogenesis of several infectious diseases. Currently, the precise mechanism by which disease-causing molecules are assembled into the outer membranes of bacteria and mitochondria is poorly understood. The knowledge that the project develops may inform future strategies aimed at the rational treatment of bacterial and mitochondrial diseases.Read moreRead less