Regulation Of Ribosomal Gene Transcription By C-MYC During Differentiation And Lymphomagenesis.
Funder
National Health and Medical Research Council
Funding Amount
$287,261.00
Summary
A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however ....A fundamental question in medical biology revolves around how cells respond to the demands to grow and produce proteins, particularly in the setting of the rapid growth of cancer cells. One of the important facets of cellular growth is the production of new proteins needed for all areas of cell life. It is well known that cellular growth involves the production of proteins and this in turn requires the transcription or duplication of ribosomal RNAs (rRNAs). The control of rRNA synthesis, however, is not well understood. We have identified a novel process to link a cancer causing gene c-MYC to the control of protein production in cells through regulation of rRNA synthesis. Our experiments will examine the hypothesis that c-MYC directly affects the production of rRNA . Finally we will test the link between the ability of c-MYC to cause malignant growth of cells and its role in increasing synthesis of rRNA. These findings may lay the basis for new treatments for disorders of regulated cell growth such as cancer.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
The Role Of The M6P-IGF-II Receptor In Regulating Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
We will investigate if a cell surface protein that suppresses the growth of breast cancer cells is also able to reduce the cancer spreading to other organs. The part of the molecule required for this effect will be identified so that smaller forms of the protein can be tested to inhibit tumour spread. Genes and proteins altered by the presence of this protein in breast cancer cells will be examined to determine how the protein suppresses tumours and to identify novel tumour markers.
Enrichment, Differentiation And Functional Analysis Of Growth Hormone Progenitor Cells From The Adult Mouse Pituitary
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH de ....Many important bodily functions including growth, metabolism, onset of puberty, fertility, lactation and the ability to cope with stress are controlled by hormones secreted by the pituitary gland. Consequently, insufficient hormone production by the pituitary gland (hypopituitarism) results in life-threatening conditions which are a significant clinical problem. Growth Hormone (GH) deficiency is the most common form of pituitary hormone deficiency, affecting 1:3,500 individuals. Currently, GH deficiency is treated by daily injections of growth hormone at a cost of $30,000 to $50,000 per patient per annum. However, even with daily injections and despite the cost, it is difficult to mimic the naturally fluctuating hormone levels in the body, resulting in incomplete growth rescue. Long term injections also have severe side effects that can lead to cardiovascular problems, abnormal bone density, diabetes and cancers of various types. To overcome the disadvantages of hormone therapy we are investigating a new cell replacement therapy to treat GH deficiency. This approach requires knowledge about the mechanism by which GH-secreting cells are generated and maintained in the adult pituitary. For the first time, we have isolated a type of progenitor (unspecialised) cell from adult mouse pituitary that is capable of dividing and generating GH-secreting cells. Our current research aims to further purify these cells and to show that they are capable of secreting GH in response to biologically relevant signals. In addition, we will test whether these cells can grow and develop into functional cells when introduced into mice. In particular, we will test whether the progenitor cells can rescue dwarfism using a mouse model of GH deficiency. This pioneering study will provide the first insight into the possibility of cell therapy for the pituitary, and may ultimately lead to the development of better therapies for patients with GH deficiency.Read moreRead less
The Roles Of Beta-catenin, APC And The Wnt/beta-catenin Pathway In Lens Development And Cataract
Funder
National Health and Medical Research Council
Funding Amount
$456,764.00
Summary
Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epi ....Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epithelial cells. However, considerably less is known about factors that regulate formation of the epithelium itself. As the epithelial cells are affected in some types of cataract it is vitally important to understand the mechanisms that control formation and maintenance of these cells. Our previous studies have identified a growth factor family (TGF-beta) that causes epithelial cataracts. Importantly, our recent studies have identified another growth factor signalling pathway (Wnt-beta-catenin) as being essential for the formation and maintenance of the lens epithelium. We hypothesise that this pathway is disrupted dring cataract formation. This project uses state of the art tools and techniques to investigate the role of two central molecular components of this Wnt pathway (APC and beta-catenin) in the developing lens. By genetically manipulating the activity of these proteins in the mouse lens we will investigate the roles these molecules and the Wnt signalling pathway play in lens development and whether inappropriate activity results in abnormal development or cataract. We will also be able to investigate whether modulating this pathway affects the formation of epithelial cataracts by TGFbeta. The results will provide detailed information on how these molecules regulate lens structure and function and have the potential to identify targets for preventing or ameliorating cataracts.Read moreRead less
Role Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Function
Funder
National Health and Medical Research Council
Funding Amount
$477,750.00
Summary
In addition to final height, growth hormone regulates many tissues in the body, and through these, regulates metabolism, body composition, vitality and aspects of ageing. However, there is some evidence that GH can also promote cancer, notably colon and blood cell cancers. Our discovery of the receptor for growth hormone in the cell nucleus, notably in many cancers, has led us to investigate the role of the nuclear GH receptor. We have found that targeting this receptor to the nucleus allows the ....In addition to final height, growth hormone regulates many tissues in the body, and through these, regulates metabolism, body composition, vitality and aspects of ageing. However, there is some evidence that GH can also promote cancer, notably colon and blood cell cancers. Our discovery of the receptor for growth hormone in the cell nucleus, notably in many cancers, has led us to investigate the role of the nuclear GH receptor. We have found that targeting this receptor to the nucleus allows the cell to divide without the need for the normal factors which initiate cell division and survival. We have also found that a part of the GH receptor acts as a gene activator, and have identified some of the nuclear proteins which bind to the receptor and make this so. This proposal aims to establish the link between the nuclear GH receptor and cell division, both mechanistically, and in live animals. We also plan to establish if nuclear localizing the receptor artificially results in cancer formation. The outcome would provide an index of risk from current GH therapy, and could lead to a new cancer therapy.Read moreRead less
Tissue Regeneration In Oral Health: Regenerating Damaged Oral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$575,833.00
Summary
The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants ....The regeneration of damaged dental tissues is an emerging area in oral health-based research and is increasingly becoming the forefront of medical-dental interdisciplinary investigations. This idea of repairing damage follows Dr Fiona Wood's unique concept of growing large amounts of specific cells in the lab and spraying them onto damaged tissue, which effectively assists in the repair of the damaged organ. This approach can be similarly used in the dental field by applying prosthetic implants with cells and growth factors, thus enhancing the regeneration of the damaged dental tissue. Artificial replacement of missing teeth has significant limitations when compared with the natural, original tissues in terms of function and appeal. Bridges and dentures have been used for centuries in dentistry but require periodic maintenance or even replacement after a period of time due to usage or loss of adaptation. Thus, if implants and bridgework can be eliminated, so too will be the problems and costs associated with them. This benefit is specifically aimed at the regional community and the public sector, as these patients are generally not in a financial position to restore missing teeth with bridgework, let alone implants. Our aims are: 1. Examine the function of two recently identified growth factors, Osteoclast-Derived Osteoblastic Factor and Emilin and Multimerin-2, through their effect on paradental in vitro cell regeneration. 2. To assess the role played by collagen bioscaffolds, together with explanted cells and growth factors examined during the in vitro studies, in the healing process by comparing teeth transplanted into an existing socket with those transplanted into a prepared site. 3. Evaluate the effect of growth factors, explanted cells and bioscaffolds on regeneration of tissues lost as a result of ligature-induced periodontal infection.Read moreRead less