The Role Of The Gastric H/K ATPase In Parietal Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$166,885.00
Summary
The cells of the body contain many specialised membrane structures. At present it is not clear how the synthesis of these stuctures is directed. To study this problem we are examining the acid secretory parietal cells of the stomach. These cells have a very elaborate membrane system that contains a major proton pump protein. By manipulating the levels and form of the proton pump we will gain novel insights into the mechanism of membrane structure and function.
The general aim of this work is to investigate the three-dimensional structures of important target proteins using X-ray crystallography. Protein crystallography is the study of the three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary ....The general aim of this work is to investigate the three-dimensional structures of important target proteins using X-ray crystallography. Protein crystallography is the study of the three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary for the complete understanding of their biological activity and is also very useful for the rational design of new drugs that may alter their activity. Approximately one third of the body's proteins are attached to membranes. However, relatively little is known about the three-dimensional structures of this important class of proteins. In this project the structures of proteins that form pores in membrane cell walls are being determined. Some of these proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. Another project involves work on a protein called GABA. The structure of GABA could lead to new drugs that control epilepsy, act as general anaesthetics, relieve anxiety and induce sleep.Read moreRead less
This proposal concerns the biochemical investigation of a protein called GABA receptor which is a known target for various anti-anxiety drugs (anxiolytics), anti-convulsants, sedatives, depressants, anti-epilespy drugs, alcohol and anaesthetics. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide essential information about how the protein works and lay the foundation for the design and development of new drugs to control epilepsy, ....This proposal concerns the biochemical investigation of a protein called GABA receptor which is a known target for various anti-anxiety drugs (anxiolytics), anti-convulsants, sedatives, depressants, anti-epilespy drugs, alcohol and anaesthetics. This work is expected to lead to the determination of the three-dimensional shape of the protein which will provide essential information about how the protein works and lay the foundation for the design and development of new drugs to control epilepsy, act as general anaesthetics, relieve anxiety and induce sleep.Read moreRead less
The activation of T lymphocytes is essential part of our immune system to fend off harmful intruders. Our research aims to understand the process of T cell activation, in particular, the contribution of fats. We found that fats create a highly ordered patch at the T cell activation site. We want to understand how lipids and proteins work together to activate T cells, how this ordered regions function in T cell activation and whether dietary lipids alter these patches and thus T cell activation.
A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, w ....A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, would enable a detailed understanding of how these protein functions. Potentially it could also aid in the development of specific inhibitors that would prevent EmrE (and perhaps other similar proteins) from carry out its harmful mission. Read moreRead less
The Role Of Membrane Condensation In T Lymphocyte Activation And Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
T cell lymphocytes are essential cells in our immune system. They respond to signals from foreign bodies to mount an immune response. Many diseases arise from errors in their activation processes. The key steps in the translation of the initial arrival of a foreign-body to a T cell into an immune response will be examined in these studies, where we will look at the cooperation of components of the cell membrane during T cell activation. This will help us to understand and treat immune disorders.
Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unkno ....Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unknown membrane proteins that move sucrose at high rates between cells and discover their transport properties. Expected outcomes are to better understand mechanisms and regulation of sucrose transport and hence provide novel opportunities to enhance crop yield. The project will foster a productive international collaboration.Read moreRead less
A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be ....Multifunctional channels as key components of biotrophic interfaces in legumes. In legumes there are two types of membrane interfaces between different genomes that are critical for growth and yield (nitrogen fixation and seed loading), which require cell-signalling pathways to control nutrient exchange. The membranes of these interfaces contain specialised proteins that form multifunctional channels through which water, uncharged molecules and electrolytes move. These channels are likely to be responsible for supporting the bulk of transported nutrients and in controlling their exchange. We aim to discover how these channels function in nitrogen fixation and seed loading with a view to developing new technologies that may enhance crop productivity.Read moreRead less
SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, ....SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, including marsupials, and on the complex roles played by a cellular structure unique to the muscle fibre, the tubular system, with respect to regulation of muscle function at physiological temperatures. The project will test hypotheses that will have far-reaching implications for muscle physiology, cell biology and evolutionary biology.Read moreRead less