Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulat ....Gene Discovery and Functional Analysis of Copper Homeostasis Genes in Drosophila. Copper is a vital nutrient required for the formation and maintenance of bones, blood vessels and the central nervous system, but copper is also potentially toxic when in excess. Homeostatic mechanisms are needed to maintain safe levels of copper in the body and disruptions to these mechanisms are associated with disorders such as Alzheimer's disease, heart disease and osteoporosis. We are investigating the regulation of a key copper pump, the Menkes protein, which helps control copper levels in the body and we are using the genetic advantages of the fruit fly Drosophila to discover new genes that regulate Menkes activity and therefore copper levels. These studies could lead to novel therapies for a range of copper-related disorders.Read moreRead less
Role Of Conformational Change In Activation Of The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that the primary event in signalling is the ability of the hormone to bring two receptors together (receptor dimerization). However, it may be that the receptor already is dimerized, and the role of the hormone is to induce a specific change in shape of the receptor, which transfers the signal of hormone binding into the cell to initiate signalling to the genome. We have good evidence that a specific shape change is required for activation of an important signalling pathway by growth hormone, and the closely structurally related receptor for erythropoietin is already dimerized before hormone binds. We want to find out exactly how the shape change acts, and whether the receptor is predimerized. This information is vital for designing small orally active mimics of growth hormone which could be of great value as an anabolic supplement for the frail elderly.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
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less
Defining in molecular terms cis-inhibition as a means to inhibit Notch signaling. Normal development of a baby and our health after birth is dependent on how our cells behave. Signals move between cells and within them to tell them what to do. Proteins interacting with other proteins mostly transmit these signals. This research focuses on a protein named Notch and the signals that it transmits. Notch functions in normal processes, such as blood vessel formation; but abnormal signaling causes and ....Defining in molecular terms cis-inhibition as a means to inhibit Notch signaling. Normal development of a baby and our health after birth is dependent on how our cells behave. Signals move between cells and within them to tell them what to do. Proteins interacting with other proteins mostly transmit these signals. This research focuses on a protein named Notch and the signals that it transmits. Notch functions in normal processes, such as blood vessel formation; but abnormal signaling causes and/or contributes to pathological situations such as degenerative disease and cancer. We are working to understand how the Notch signal is made and how to control it when it is abnormal. This will allow new medications to be developed to help people who have cancer and other Notch-related illnessesRead 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.
Structural Studies On Cell Signalling Via The LIF Receptor And Gp130
Funder
National Health and Medical Research Council
Funding Amount
$453,943.00
Summary
The cytokines play important roles in the immune system during blood cell development and inflammation, and in nerve growth, bone remodeling, reproduction and heart development. Cell responses are initiated by a cytokine bringing together on the cell surface a receptor complex made up of multiple molecules. This project will investigate the atomic structure of the cell surface macromolecular complex, and hence the underlying mechanism by which cytokine signals are initiated.
How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biol ....How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biology, and will increase our understanding of diseases that arise due to aberrant tissue growth, such as cancer. Our research findings will thus be of substantial national benefit, given that cancer is now the biggest cause of death in Australia, and that more than 88,000 Australians are diagnosed with cancer each year. Read moreRead less