Inside our cells is a complex traffic system. The vehicles are vesicles that come in different shapes and sizes and travel to specific destinations in the cell to deliver cargo such as: surface growth factor receptors that are to have their signalling terminated, proteins and lipids destined for the cell wall for growth or development (like neurite outgrowth) and proteins and hormones destined for secretion (like neurotransmitter release). More than 100 human genetic disorders map to defects in ....Inside our cells is a complex traffic system. The vehicles are vesicles that come in different shapes and sizes and travel to specific destinations in the cell to deliver cargo such as: surface growth factor receptors that are to have their signalling terminated, proteins and lipids destined for the cell wall for growth or development (like neurite outgrowth) and proteins and hormones destined for secretion (like neurotransmitter release). More than 100 human genetic disorders map to defects in one of the components of this system. Proteins called small GTPases provide order for this traffic and allow specific cargo to reach specific destinations. They regulate cell functions by acting as switches, turning biochemical processes on and off inside the cell. Ral is a small GTPase enzyme found in brain and broadly distributed in other cells. We have discovered that Ral is part of a large signalling complex. When activated Ral stimulates effectors, either the exocyst or RalBP1. In turn, mild oxidative stress controls a Ral inhibitor protein called ERp57. The research proposed aims to establish the functional role for the Ral signalling complex in cells. We will determine with which vesicle trafficking events Ral is associated, which effector it utilises in that pathway, and how that effector directs the traffic. We will also map the steps that may lead to inactivation of Ral via ERp57 in cells, and propose that this is mediated by mild oxidative stress. Techniques of molecular biology, biochemistry, molecular biology, proteomics and microscopy will be used to establish these functions. The research will lead to increased knowledge of the significance of this protein to cellular and particularly neuronal cell function. This forms the basis for understanding normal cell function and for identification of further factors causing diseases of vesicle transport. In time, such research aids in the development of specific therapies for sufferers of such diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454170
Funder
Australian Research Council
Funding Amount
$187,341.00
Summary
Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellula ....Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellular processes in plants, animals and humans. Understanding these mechanisms will provide the basis for improved management of the environment and pathological conditions through identifying molecular targets for diagnosis, genetic manipulation or drug design.Read moreRead less
Regulation Of Hedgehog Signalling Through Intracellular Trafficking Events
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which ....The hedgehog signalling cascade plays a role in forming almost every organ of the body during development of an embryo. Perturbation of the function of key members of this pathway during embryonic development often results in death in utero or severe childhood abnormalities. In addition, disruption to this pathway also results in a range of cancers, most notably the extremely common skin cancer basal cell carcinoma. In this proposal we aim to investigate in detail the regulatory mechanisms which operate to ensure that this complex pathway of interacting molecules functions correctly during embryonic development. By understanding how this regulation occurs we will gain valuable insight into how disruption of this pathway results in such a range of disease, as well as into how agents which modulate this pathway may potentially act in a therapeutic setting.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561173
Funder
Australian Research Council
Funding Amount
$207,189.00
Summary
High throughput proteomics - Thermo Finnigan ProteomeX LCQ Integrated Proteomics Workstation. As research in the biological sciences moves into post-genomics era, so attention has focused on the development of technologies capable of characterizing the molecular complexity inherent in the proteome. Recent technical innovations in this field have resulted in the advancement of mass spectrometers that are capable of exemplifying unknown proteins with great efficiency. These new technologies are ....High throughput proteomics - Thermo Finnigan ProteomeX LCQ Integrated Proteomics Workstation. As research in the biological sciences moves into post-genomics era, so attention has focused on the development of technologies capable of characterizing the molecular complexity inherent in the proteome. Recent technical innovations in this field have resulted in the advancement of mass spectrometers that are capable of exemplifying unknown proteins with great efficiency. These new technologies are central to any institution committed to the development of a competitive research nexus in biological sciences. The purpose of this application is to upgrade the mass spectrometry facility at the University of Newcastle such that it is able to provide cutting edge support to the extensive scientific community within the Hunter region.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668266
Funder
Australian Research Council
Funding Amount
$264,000.00
Summary
High Resolution Cellular and Molecular Imaging System. Understanding where molecules are within cells, and how they interact with each other, is fundamental to significant advances being made in biology. Our research will use advanced imaging techniques to localize proteins within a variety of cells including neurons and germ cells. We will be able to determine how the different molecules within a single cell interact with each other. This information is relevant to many biological mechanisms ....High Resolution Cellular and Molecular Imaging System. Understanding where molecules are within cells, and how they interact with each other, is fundamental to significant advances being made in biology. Our research will use advanced imaging techniques to localize proteins within a variety of cells including neurons and germ cells. We will be able to determine how the different molecules within a single cell interact with each other. This information is relevant to many biological mechanisms and to many human diseases. Furthermore, our research will help maintain Australia's strong international reputation in the fields of neuroscience, protein trafficking and stem cells. Read moreRead less
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less
Socs proteins in development and disease. Socs proteins are a component of a pathway that is central to a range of developmental processes, including embryonic development. In addition, there is evidence that these proteins are perturbed in several disorders. This Project will enhance our understanding of the Socs proteins and their role in disease, and ultimately provide an opportunity to identify new therapeutic strategies.
Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiati ....Molecular signals that regulate the regenerative properties of intestinal epithelial cells. Most cancer deaths are due to the cancer spreading to other organs. Cancer is much more difficult to treat once it has spread to other organs in the body where the cancer cells can exist in a dormant state. Dormant cancer cells evade conventional anticancer treatment and can remain dormant for a very long time before they change back to a 'tumour-growing' state. An understanding of how the cancer initiating (stem cell) property of tumour cells is maintained offers potential novel avenues to eliminate persistent cancer cells. This knowledge will ultimately lead to better management and treatment of cancer, and increase survival. An understanding of stem cell behaviour is also central to the control of degenerative conditions.Read moreRead less
The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims t ....The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims to look at the mechanisms that exist to prevent this initial loss of genetic material within an individual cell. It further aims to translate theses discoveries into the clinic, providing new tools for diagnosis and prognosis of specific cancers and to establish links with major pharmaceutical companies to develop novel anticancer therapies.Read moreRead less