Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable ....Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable us to develop a computational model of the vascular wall and so predict how changes in electrical properties, as occur during pressure changes, can influence blood flow. Since ageing is accompanied by an increase in blood pressure, our results will contribute to a better understanding of blood flow regulation in our ageing population.Read moreRead less
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-r ....New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-resilient root systems. Importantly, we have discovered specific molecules that either promote or inhibit blood vessel formation. A better understanding of how these molecules work could lead to novel treatments for cancer or cardiovascular disease.Read moreRead less
How do nano-molecular carboxysome protein structures function in alpha and beta-cyanobacteria and can we use them for novel reaction compartmentalisation? In blue-green algae, protein nano-structures, known as carboxysomes, act as tiny compartments where carbon dioxide (CO2) can be fixed into simple sugars at high efficiency. This important photosynthetic process forms the basis of global primary productivity on this planet, but most land-based CO2 fixation lacks the efficiency seen in blue-gree ....How do nano-molecular carboxysome protein structures function in alpha and beta-cyanobacteria and can we use them for novel reaction compartmentalisation? In blue-green algae, protein nano-structures, known as carboxysomes, act as tiny compartments where carbon dioxide (CO2) can be fixed into simple sugars at high efficiency. This important photosynthetic process forms the basis of global primary productivity on this planet, but most land-based CO2 fixation lacks the efficiency seen in blue-greens. This research aims to determine how the proteins that make up carboxysomes are 3-dimensionally arranged and how these structures function to enhance rates of CO2 fixation. A more thorough understanding of the carboxysome is likely to have potential applications in industrial nano-technology and improve our understanding of oceanic primary productivity.Read moreRead less
Photosynthetically active bicarbonate transporters from cyanobacteria & their rational redesign for application in engineered crops that use less water. Marine blue-green algae are critical components of global primary productivity and fisheries productivity but CO2 acquisition processes in these organisms are poorly understood. Our aim is to determine the protein structure and regulatory controls present in two classes of cyanobacterial bicarbonate transporters that are required for efficient p ....Photosynthetically active bicarbonate transporters from cyanobacteria & their rational redesign for application in engineered crops that use less water. Marine blue-green algae are critical components of global primary productivity and fisheries productivity but CO2 acquisition processes in these organisms are poorly understood. Our aim is to determine the protein structure and regulatory controls present in two classes of cyanobacterial bicarbonate transporters that are required for efficient photosynthesis. This information is now critical to the our goal of redesigning these bicarbonate transporters so they will be functional in plants, thereby contributing to the applied objective of engineering crop plants that could produce good grain yields with reduced water requirements.Read moreRead less
Active bicarbonate transporters from cyanobacteria: physiological properties, genetic regulation, and introduction into plants for crop improvement. An intriguing set of membrane transport proteins that accumulate bicarbonate into marine cyanobacterial cells will be investigated. These proteins support the crucial process of photosynthetic carbon dioxide fixation in marine cyanobacteria (blue-green algae), which are major contributors to global carbon dioxide sequestration and form one of the f ....Active bicarbonate transporters from cyanobacteria: physiological properties, genetic regulation, and introduction into plants for crop improvement. An intriguing set of membrane transport proteins that accumulate bicarbonate into marine cyanobacterial cells will be investigated. These proteins support the crucial process of photosynthetic carbon dioxide fixation in marine cyanobacteria (blue-green algae), which are major contributors to global carbon dioxide sequestration and form one of the foundations of the marine food web. These bicarbonate "transporters" will also be transferred into a model plant system to test whether the efficiency of photosynthesis can be improved, with corresponding gains in the water-use efficiency of these plants. If successful this technology will have profound global implications for improving crop production in semi-arid areas.Read moreRead less
The structure and function of cyanobacterial carboxysome multi-protein complexes and their role in carbon sequestration in cyanobacteria. Cyanobacteria are important contributors to global photosynthesis and have evolved unique mechanisms for capturing CO2 from their aquatic environments. Understanding these molecular mechanisms is important for both predicting how cyanobacteria affect carbon fixation at the global scale, and how their genetic specialisation may be used for improving photosynthe ....The structure and function of cyanobacterial carboxysome multi-protein complexes and their role in carbon sequestration in cyanobacteria. Cyanobacteria are important contributors to global photosynthesis and have evolved unique mechanisms for capturing CO2 from their aquatic environments. Understanding these molecular mechanisms is important for both predicting how cyanobacteria affect carbon fixation at the global scale, and how their genetic specialisation may be used for improving photosynthesis in agricultural plants. This project aims to examine one particular aspect of this specialisation, the multi-protein carboxysome complex, where CO2 fixation occurs. Using recent whole-genome information we will take a proteogenomic approach to understanding the structure and function of the carboxysome and how it contributes to the photosynthesis of the cell.Read moreRead less
Nano-molecular structure and function of protein mini-compartments known as carboxysomes. Intriguing protein nano-structures, present in blue-green algae and known as carboxysomes, act as tiny compartments where CO2 can be fixed into simple sugars at high efficiency. This important photosynthetic process forms the basis of global primary productivity on this planet, but most land-based CO2 fixation lacks the efficiency seen in blue-greens. This research aims to determine how the several proteins ....Nano-molecular structure and function of protein mini-compartments known as carboxysomes. Intriguing protein nano-structures, present in blue-green algae and known as carboxysomes, act as tiny compartments where CO2 can be fixed into simple sugars at high efficiency. This important photosynthetic process forms the basis of global primary productivity on this planet, but most land-based CO2 fixation lacks the efficiency seen in blue-greens. This research aims to determine how the several proteins that make up carboxysomes come together to makeup carboxysome nano-structures and how these function to enhance rates of CO2 fixation. A more thorough understanding of the carboxysome is likely to have potential applications in industrial nano-technology and improvements in crop productivity.Read moreRead less