Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less
The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less
Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes i ....Making peptides orally bioavailable. Bioactive peptides are exceptionally useful molecules, however to fully realise their exciting applications key limitations need to be overcome: they can't be delivered orally and they do not last long in the body. This project aims to develop a molecular tag that can dramatically enhance both the oral absorption and time in the body of a peptide. This will include identifying the key elements of the tag required for function, the breadth of peptide cargoes it can be applied to and the mechanisms underlying this technology. The outcomes of this project will facilitate the future development of peptides for biotechnology, pharmaceutical and veterinary applications.Read moreRead less
The Molecular Mechanism Of Ion-coupled Transport In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$441,407.00
Summary
Cells in the brain communicate through chemical signals called neurotransmitters. Neurotransmitter transporters reside in the membranes of cells and are responsible for regulating levels of these chemicals in the brain. They play an important role in the normal function of the human brain but their dysfunction is responsible for many diseases including Alzheimer's disease and motor neuron disease. It is crucial to understand how these proteins work in both normal and disease states.
Defining The Mechanism Of Assembly Of Herpes Simplex Virus In The Neuronal Growth Cone And Its Subsequent Exit To Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$774,624.00
Summary
Herpes simplex virus (HSV) causes dormant infection of nerve cell bodies near the spine. It periodically reactivates to be transported along nerves to the skin where it causes oral, genital or neonatal herpes and mediates HIV superinfection. HSV assembles into its final form in the terminal part of the axon just prior to crossing into skin. Elucidating the mechanism of HSV assembly and exit will facilitate new strategies for antiviral agents and immune treatment for HSV and similar viruses.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
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
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