Correlative Structure-function Studies Of Cis- And Trans-Golgi Membrane Traffic In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$649,531.00
Summary
This project combines imaging by light and electron microscopy with additional techniques for studying protein function at the molecular level, to elucidate how changes in the 3D organisation of cellular machinery can lead to fundamental changes in the function and health of mammalian cells. Although this work includes detailed investigation of the 'insulin factory', it has the potential to modify established concepts on membrane traffic and protein secretion well beyond the field of diabetes.
Identification And Characterization Of Novel Proteins In Endosomal Cholesterol Transport
Funder
National Health and Medical Research Council
Funding Amount
$540,636.00
Summary
Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against hea ....Abnormal subcellular distribution of cholesterol is associated with a number of common diseases including heart disease and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize novel molecules that regulate the transport of intracellular cholesterol. Results from the proposed studies will provide important insights into the molecular mechanisms governing intracellular cholesterol transport and distribution, and will lead to better treatment strategies against heart disease and dementia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100004
Funder
Australian Research Council
Funding Amount
$540,000.00
Summary
An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and ....An automated 3D electron microscopy facility. An automated 3D electron microscopy facility: The aim of this project is to establish the next generation of electron microscopy facility, with a fully automated tool enabling 3D imaging. The automated serial section system incorporated in a scanning electron microscope circumvents the limitation of transmission electron microscopy, which provides unique insights into molecular structures and cell components at high resolution, however, the area and volume are limited in size to a few microns. This new type of microscope can image whole organisms and be used by non-electron microscopists. It will be housed in an open access facility and will meet a growing demand for 3D electron microscopy.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoin ....Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoing and healthy association at the cellular level. Unlike some terrestrial symbioses, little is known about the structure and function of the coral symbiosome. This study sets out to investigate this membrane at the cellular and molecular level.Read moreRead less
Sugars in the real world: are cultured cancer cells a good model system for studying protein glycosylation? It is challenging to study errors in metabolism in human beings, so researchers use cells grown in the laboratory to understand disease processes. This project will determine if cultured cells accurately reflect the real changes to cell surface sugars that occur in all cancers, and the effect of these changes on the invasive properties of colon cancer cells.
The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of ....The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of cellular networks in higher organisms such as cell polarisation, directed migration, metabolism and autophagy. Vertebrates have evolved mechanisms for joining individual Golgi stacks into a ribbon structure. The relevance of this ribbon structure remains a mystery. The project aims to answer this major question in cell biology.Read moreRead less
Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potent ....Identifying genes controlling the regulatory and metabolic interactions between the energy organelles of the leaf. Plant energy metabolism underlies the synthesis of many important products in crops, and subtle changes in metabolism can enhance key plant traits, such as germination rates, early seedling vigour, biomass/yield, and tolerance to harsh environments. Furthering our understanding on the complex interplay of genes controlling energy metabolism and its impact on leaf function has potential outcomes for smart genetic manipulation either by classical breeding or genetic transformation. There are more than 10,000 genes of unknown function in plant genomes and this represents a tremendous untapped resource for future Australian R&D outcomes and insights from this research proposal will have application to all plant-based agriculture.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
NMR Of Red Cells: Plasma Membrane Oxidoreductase, And Cation Transport
Funder
National Health and Medical Research Council
Funding Amount
$192,388.00
Summary
An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknow ....An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknown; neither is the immediate source of the reducing equivalents (electrons) known. Novel, non-invasive, 13C NMR methods have been developed, and others are planned in this project, to study the rate of reduction of Otest? compounds, including 13C-ferricyanide, and reactions of 13C-ascorbate. This will provide a quantitative understanding of the kinetics of the redox reactions in the intact cell. The transfer of negative charges (electrons) from the cell, in the longer term (minutes) inevitably must be matched by the movement of cations (positive charges). The main cation flux is mediated by Na+, K+-ATPase, but various cation exchange pathways are also involved in the total Oionic economy? of the cell. Of special interest will be the calcium-activated K+ (or Gardos) channel. This Oopens? inappropriately in malaria, sickle cell anaemia, and under blood bank storage conditions, and this is thought to be the basis of some of the pathological events in these conditions. The alkali-metal cation exchange pathway ( Na+-Li+) is more activate in the red cells of many patients with hypertension. So, multiple-quantum NMR methods will be used to monitor membrane transport and binding of cations to characterise the kinetics and regulation of the K+-channel, and the Na+-Li+ exchange reactions. The significance will lie in a basic understanding of, and possible 'diagnostic methods' for the biochemical processes that occur in red blood cells in health and disease.Read moreRead less