Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101648
Funder
Australian Research Council
Funding Amount
$363,000.00
Summary
A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised gro ....A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised growth factor signalling, using the sophisticated genetic and advanced imaging methods possible in the fruit fly Drosophila. This project aims to understand growth factor control as its deregulation leads to serious developmental disorders and diseases.Read moreRead less
Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understandin ....Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understanding of olfaction in insects, increased national and international collaboration, and outstanding graduate student training. This research will be of significant future benefit in deriving methods to modify the behaviour of insects of agricultural or medical importance, for example the sheep blowfly. Read moreRead less
Functions Of A Novel Conserved DNA Damage Response Protein Family In Telomere Stability
Funder
National Health and Medical Research Council
Funding Amount
$282,825.00
Summary
The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, c ....The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, chromosome ends are covered by a cap, which hides them from the DNA damage response machinery. From these considerations it is clear that there are close connections between the cellular DNA damage response and chromosome ends. Moreover, recently it has become clear that DNA damage proteins are also required to stop normal cells from growing, a process termed senescence. Senescence is a consequence of shortened chromosome ends, and does not occur in cancer cells. Altogether, it is clear that DNA breaks and senescence are two of the major questions for our understanding of cancer development. We have identified a novel conserved protein family that is involved in the response to DNA damage in yeast and humans. In addition, the yeast Mdt1 protein is a very sensitive indicator of changes in the telomere cap. Absence of proteins that organise the cap leads to the addition of several phosphate groups to the Mdt1 protein. We propose that phosphate-coupled Mdt1 prevents chromosome ends from fusion with each other, or from fusing with broken DNA ends after widespread damage. As a consequence, cells that have mild cap defects die at an >1000-fold increased rate in response to DNA damage when they also lack Mdt1. As part of this application we want to find out the precise mechanism by which Mdt1 stabilises chromosome ends, and test our hypothesis that the corresponding human protein termed ASCIZ also has similar functions in protecting chromosome ends.Read moreRead less
A novel regulator of growth signalling in Drosophila. This project aims to increase understanding of how growth is regulated by growth factor hormones. In animals, growth is controlled by signalling pathways that are activated by secreted peptide hormones. A new regulator of growth in the fruitfly Drosophila, the membrane attack complex/perforin-like (MACPF) protein Torso-like, has been identified. The project aims to unravel how Torso-like functions to regulate growth, thus throwing light on th ....A novel regulator of growth signalling in Drosophila. This project aims to increase understanding of how growth is regulated by growth factor hormones. In animals, growth is controlled by signalling pathways that are activated by secreted peptide hormones. A new regulator of growth in the fruitfly Drosophila, the membrane attack complex/perforin-like (MACPF) protein Torso-like, has been identified. The project aims to unravel how Torso-like functions to regulate growth, thus throwing light on the role this protein family may play in all animals. The findings are expected to provide key insights into the modification of growth factor activity, which is often dysregulated in human cancers and growth disorders, and may enable the design of new strategies for interfering with insect development for pest control.Read moreRead less
The evolution of Membrane Attack Complex / Perforin-like proteins in development and immunity. Membrane Attack Complex/Perforin-like (MACPF) proteins commonly play key roles in vertebrate immunity, however some family members play critical but poorly understood developmental roles. It has been shown that the sole Drosophila MACPF protein, Torsolike, plays both developmental and immune roles. Here the aim to unravel how Torsolike functions in these dual roles by using a novel genetic screening ap ....The evolution of Membrane Attack Complex / Perforin-like proteins in development and immunity. Membrane Attack Complex/Perforin-like (MACPF) proteins commonly play key roles in vertebrate immunity, however some family members play critical but poorly understood developmental roles. It has been shown that the sole Drosophila MACPF protein, Torsolike, plays both developmental and immune roles. Here the aim to unravel how Torsolike functions in these dual roles by using a novel genetic screening approach to identify genes needed for its function. The project also uses comparative studies to probe alternative functions of Torsolike in a second insect, the honeybee. This data will be pivotal for understanding how members of this family have evolved into proteins that are separately involved in immune defense and in development in higher vertebrates.Read moreRead less
Membrane attack complex/perforin-like proteins in developmental and neurobiology. This project will aim to use the fruit fly as a model system to understand how members of the perforin-like superfamily, a family of proteins more usually associated with mammalian immunity, function in embryonic and neural development. These data will eventually provide central insight into human diseases such as cancer and autism spectrum disorder.
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the ....Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the most fundamental questions in the whole of biology: what is the basis for the primal distinction between sex and soma?Read moreRead less
How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. ....How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. This research will continue Australia's high profile in reproductive biology using one of our iconic native mammals. A greater understanding of marsupial reproduction will also contribute to management of our threatened marsupial populations.Read moreRead less