Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.Read moreRead less
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
I am an academic endocrinologist and clinician. I lead a large research program that investigates the links between hormones and diseases of ageing in women. Thus my research program addresses the contribution of changes in adrenal and ovarian steroids in
Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
Australian art exhibitions 1968-2009: a generation of cultural transformation. The years 1968 to 2009 witnessed a transformation in the way Australians saw the art of their country. This project investigates the impact of increased funding (government and private) and new scholarship on the curating of art exhibitions, and traces the reconfiguration of Australia’s art history that took place in exhibitions during this period.
A national framework for managing malignant plastics in museum collections. A national framework for managing malignant plastics in museum collections. This collaborative project between three universities, four museums and an art gallery aims to discover how to predict and increase the lifespan of malignant plastics or polymers by studying their identification, deterioration and conservation. 5 to 80% of museum collections, composed of growing numbers of plastic or polymer-based materials, need ....A national framework for managing malignant plastics in museum collections. A national framework for managing malignant plastics in museum collections. This collaborative project between three universities, four museums and an art gallery aims to discover how to predict and increase the lifespan of malignant plastics or polymers by studying their identification, deterioration and conservation. 5 to 80% of museum collections, composed of growing numbers of plastic or polymer-based materials, need better preservation. Conservators do not have much expertise in preserving plastics, which are contemporary and have a relatively short life expectancy. This project intends to provide museums with a model for prioritising and effectively allocating resources to preserve a vulnerable group of collections for future generations.Read moreRead less
The invisible farmer: Securing Australian farm women's history. The invisible farmer: Securing Australian farm women's history. This project, believed to be the first national study of farm women in Australia, aims to address their historical and contemporary invisibility by creating an online, publicly accessible, multimedia documentary database that maps the role women play/played in Australian agriculture. Chief investigators in the fields of social work, women's history, cultural informatics ....The invisible farmer: Securing Australian farm women's history. The invisible farmer: Securing Australian farm women's history. This project, believed to be the first national study of farm women in Australia, aims to address their historical and contemporary invisibility by creating an online, publicly accessible, multimedia documentary database that maps the role women play/played in Australian agriculture. Chief investigators in the fields of social work, women's history, cultural informatics and archival practice will collaborate with community, government and cultural organisations to create digital tools for research, public access and community engagement. Reframing the narrative of rural Australia is expected to create greater understanding and awareness of the value of inclusion, reveal structures of gender inequality in rural communities, and enable significant outcomes in research, industry and public policy.Read moreRead less
Selective Estrogen Receptor Modulators (SERMs) - A Potential New Treatment For Women Of Child-bearing Age With Psychotic Symptoms Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$210,480.00
Summary
Schizophrenia is a devastating illness urgently requiring a new treatment approach. We have discovered that estrogen is an effective treatment for women with schizophrenia and are currently trialling a safer Selective Estrogen Receptor Modulator (SERM) known as brain estrogen� in postmenopausal women with schizophrenia. Regulatory permission is now available to trial the SERM in younger women, and we seek to extend our current SERM study into child bearing age women with schizophrenia.