Effect Of Prostaglandin E2 On The Periodontium And Alveolar Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is pl ....Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is placed in contact with mandibular bone, adjacent to erupted teeth, new bone and cementum formation occurs. The ability of PGE2 to induce new bone formation indicates a potential use for PGE2 in the management of bone loss associated with periodontal diseases, and the formation of new bone around dental implants, and around teeth following orthodontic movement. Growth factors are active in healing and have valuable applications in augmenting wound repair. Osseous and dental tissues are rich in growth factors, and these factors are involved with the regulation of bone metabolism as well as tissue repair, thus the action of PGE2 on the periodontium is most likely regulated via these factors. Since regeneration of the periodontium is a fundamental goal of dentistry, any treatment which leads to predictable formation of new connective tissues and their long term stability would be a major clinical advance.Read moreRead less
Epidermal Growth Control In Psoriasis And Normal Skin
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to th ....Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to the outside. In normal states and when responding to injury or disease, this cell turnover speed can be finely tuned, for example accelerated in the case of a healing wound. In contrast, if damaged by the sun, epidermal cells undergo a form of cell suicide (apoptosis) to prevent tumours forming from cells with damaged genes. This changing turnover speed is controlled by a series of growth factors, or cytokines. Insulin-like growth factor-I (IGF-I) is a unique cytokine that can control both cell turnover rate, and cell death. We aim to uncover the complex biochemical interactions that allow the epidermal IGF-I system to achieve this seemingly contradictory task. This study is important because when the epidermis loses the ability to finely tune its turnover speed, ulcers, sun damage, the common skin disorder psoriasis, or worse still, skin tumours, arise. This project explores ways of manipulating the IGF-I system to prevent this, and builds on some technology developed by the research group that has already proven effective in the control of psoriasis. The project also promises to discover undiscovered growth regulators that could be used in new gene therapies for skin overgrowth diseases.Read moreRead less
Insulin-like Growth Factor Binding Protein-2 Is A Crucial Activator Of Aggressive Behaviour In Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
The insulin-like growth factor (IGF) system, required for normal development and adult life, is often altered in many diseases including cancer. Key regulators of the IGF system are the IGF binding protein (IGFBP) of which IGFBP-2 is the 2nd most abundant. IGFBP-2 may enhance or inhibit the IGFs, but the mechanisms are not clear. This proposal aims to dissect IGFBP-2 action with the ultimate goal to provide knowledge for the development of targeted therapeutic modulators of IGFBP-2 activity.
Role Of Insulin-like Growth Factor Binding Protein-3 As A Mediator Of Apoptosis In Human Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$352,234.00
Summary
Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cance ....Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cancer progression. IGFBP-3 inhibits the growth of breast cancer cells and causes them to die by a process called apoptosis. We are determining how IGFBP-3 causes breast cancer cells to die by apoptosis. In particular, we are investigating whether IGFBP-3 may make breast cancer cells more sensitive to the apoptotic effects of ionising radiation and chemotherapeutic drugs which are both current therapies for the treatment of breast carcinoma. These studies may, in turn, elucidate the mechanisms that lead to increased resistance of breast cancers to these treatments.Read moreRead less
Insulin-like Growth Factor (IGF) -II, Cytotrophoblast Migration And Placental Development
Funder
National Health and Medical Research Council
Funding Amount
$487,750.00
Summary
During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs i ....During pregnancy, placental cells invade into the uterus and tap into the maternal blood vessels to procure an adequate blood supply for the growth of the placenta and hence the fetus. If this invasion process is impaired early in pregnancy, then the woman may suffer a miscarriage, if the process is impaired in mid-pregnancy then the mother may develop preeclampsia in which her blood pressure goes up and, in severe cases, placing her life and that of her unborn baby at risk. Miscarriage occurs in 10-15% of pregnancies and preecclampsia in 7% of pregnancies. Preecclampsia may be life-threatening in up to 3% of all pregnancies and is a major cause of maternal death in pregnant women in Western countries. This project will examine the effect of treatment of the pregnant guinea pig with insulin-like growth factor-II on placental cell invasion and the capacity of the placenta to deliver nutrients to the fetus. We will also determine whether the effects of this treatment are mediated by a specific membrane receptor on the cell surface of the invading placental cells. We predict that this growth factor will enhance placental cell invasion and improve placental function. If this is the case then our findings may be developed for use in women at risk, to improve placental function and hence maternal and fetal health.Read moreRead less
Insulin-like Growth Factor (IGF)-II Binding Specificity Of IGF Binding Protein-6: Structural And Functional Studies.
Funder
National Health and Medical Research Council
Funding Amount
$265,630.00
Summary
Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like ....Insulin-like growth factor II (IGF-II) is a protein which is involved in normal growth. However, in some circumstances it may also stimulate cancer growth. IGF binding protein-6 (IGFBP-6) binds to IGF-II and stops its activity. One of the major challenges of modern biology is understanding why some proteins bind to other proteins. Proteins fold in various ways and have specific three-dimensional structures. Two proteins which bind strongly to each other have structures which fit each other like a 'lock and key'. The aim of this project is to understand how IGFBP-6 binds to IGF-II by looking at its three-dimensional structure. Using this information, it may be possible to develop new treatments which can inhibit IGF-II activity and therefore may be useful in the treatment of some cancers.Read moreRead less
Interactions Between IGFBP-3 And TGFbeta In The Inhibition Of Breast Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$662,970.00
Summary
A protein first identified by our research group, called insulin-like growth factor binding protein-3 or IGFBP-3, has been shown to be a potent inhibitor of the growth of cancer cells. High levels of IGFBP-3 in the bloodstream are associated with a decreased risk of several cancer types, including breast cancer. However, the way in which this protein prevents cancer cells from growing is poorly understood. This project will investigate an entirely novel idea, developed in our laboratory, that th ....A protein first identified by our research group, called insulin-like growth factor binding protein-3 or IGFBP-3, has been shown to be a potent inhibitor of the growth of cancer cells. High levels of IGFBP-3 in the bloodstream are associated with a decreased risk of several cancer types, including breast cancer. However, the way in which this protein prevents cancer cells from growing is poorly understood. This project will investigate an entirely novel idea, developed in our laboratory, that the actions of IGFBP-3 are intimately connected with the actions of another known cell growth inhibitor called transforming growth factor beta (TGFbeta). We have found that these two proteins initiate the same sequence of events leading to growth inhibition in breast cancer cells, and that a receptor protein required for TGFbeta activity is also needed for IGFBP-3 to be inhibitory. Our work has the potential to explain for the first time exactly how IGFBP-3 stops cancer cells from growing. This is important because it is an abundant protein in the body, and understanding how it acts may lead to the development of new approaches to cancer therapy that exploit our findings.Read moreRead less
Diagnostic Tests To Predict Risk For Life Threatening Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$682,824.00
Summary
The main complications of pregnancy, preeclampsia, preterm birth and intrauterine growth restriction afflict 19% of first pregnancies and are life threatening to the mother or baby in 6% of pregnancies. Currently we have no way of knowing which women will suffer these diseases until symptoms manifest. We aim to develop genetic tests that can predict which women are at risk. This will permit earlier interventions that will improve the health of pregnant women and their babies.