The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the different transcription factors in the Hippo pathway operate to control tissue growth. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Mechanisms For Regulation Of Myc Transcription And Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$645,347.00
Summary
We aim to use the animal model system, the vinegar fly, to investigate mechanism for cancer initiation. The fly has been studied for over 90 years and has proved an excellent genetic model for understanding the complex processes leading to abnormal cell growth, which is associated with the early stages of human cancer. The high level of conservation between fly genes and human cancer genes means these studies will provide novel insights into the genetic mechanisms underlying tumour formation.
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem cells.
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
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
Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
UNDERSTANDING THE MOLECULAR MECHANISMS CONTROLLING NUCLEOLAR SURVEILLANCE IN DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$855,972.00
Summary
Alterations in the ability of cells to make ribosomes, the cellular factories that make protein, contribute to a range of diseases including cancer and a class of inherited disorders called ribosomopathies that are rare but largely untreatable. These changes cause disease by controlling the “nucleolar surveillance pathway” that causes cells to either stop dividing or die. Here we propose to identify new genes that regulate this pathway to identify new targets for treating these diseases.
Determining recurrence risk in breast cancer is crucial, as more than half of all recurrences occur after 5 years. However, optimal management of breast cancer is hampered by the challenges in finding rational preventative and predictive targets. Our vision is to find targets responsible for progenitor cell expansion, as candidates for prevention, and to find markers of relapse, to predict early versus late responders to therapy.
Understanding The Biological Regulation Of MLKL And Its Role In Necroptotic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$656,979.00
Summary
Cell death is a normal process that permits the growth and defence of our vital tissues. One kind of cell death, necroptosis, is characterized by the swelling and bursting of cells. When cells ‘explode’ in this uncontrolled way they provoke an inflammatory response. This may be a factor behind illnesses ranging from colitis to cardiovascular disease. Understanding necroptotic cell death may pave the way for new therapies for those that suffer from these devastating conditions.