In Vivo Modelling Of WIF1 In Bone Development And Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$402,796.00
Summary
Osteosarcoma is the most common primary cancer of the bone. We identified Wnt inhibitory factor 1 (WIF1), a secreted protein that inhibits the Wnt cell growth pathway, to be silenced in osteosarcoma. We propose to investigate the role of WIF1 in normal development, how its loss contributes to cancer progression, and whether treatment with WIF1 protein can inhibit tumour growth. Our overall aim is to discover key molecules, which can be targeted therapeutically to inhibit osteosarcoma growth..
E2F Inhibitors As Anticancer Agents For Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour de ....Squamous cell carcinoma of the head and neck is one of the six most frequent causes of cancer death worldwide. these tumours are currently treated with surgery, radiotherapy and chemotherapy. Although these treatments are associated with a five year survival rate of between 40% and 60% there is a critical need for more effective and less destructive treatments. In this application we will extend on our earlier work in which we identified the protein E2F1 as being a major contributor to tumour development. In normal cells, E2F1 is required for the regulated growth of head and neck cells. However, we found that in head and neck tumours, E2F1 is overactive and contributes to the dergulated growth of the tumour. In this project we will test our newly developed inhibitors of E2F1 on various tumour cells derived from head and neck cancers to see how effective they are at stopping tumour cell growth. Furthermore we will test these compounds in animal models of head and neck cancer to determine whether they will be useful therapeutic agents for treatment of human cancer. Early results on tumour cell lines look very promising.Read moreRead less
Barrett's Oesophagus And Reflux Oesophagitis : Efficacy Of Medical Vs Surgical Management
Funder
National Health and Medical Research Council
Funding Amount
$510,750.00
Summary
Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of canc ....Gastro-oesophageal reflux disease is very common. In some people it leads to oesophageal cancer, which is increasing in incidence more rapidly than any other cancer in the developed world. Significant resources are required for its diagnosis, surveillance and treatment. There are two main forms of treatment, acid suppressing drugs which may be required for the rest of the person's life, or surgery. The goal of treatment is the control of the symptoms such as heartburn, and the prevention of cancer. It is relatively easy to determine if the symptoms are controlled, and both medical and surgical treatments do this. It is not as easy to measure if a treatment will reduce the risk of cancer, because it takes so long to develop. We will compare a group of patients with reflux disease treated with drugs with a group treated by surgery. In each group we will take oesophageal tissue before treatment and compare it with similar tissue taken after treatment. We will look for reductions in abnormal cells and genes that are in diseased tissue and are important in the development of cancer. This study will help us understand the mechanisms by which reflux causes damage to the oesophagus and how it ultimately leads to cancer. We will learn if medical or surgical treatment is better in healing the underlying damage in the oesophagus, and which treatment is more likely to prevent cancer developing. It may result in more effective management of reflux in our community and help reduce the number of cases of oesophageal cancer.Read moreRead less
C-Kit Signalling And Cellular Responses In Haemopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$731,115.00
Summary
Growth factors acting on cell surface receptors activate multiple intracellular signalling pathways that regulate cellular growth and function. Mutations in the genes that code for these receptors or their downstream signalling pathways contribute to many human cancers. The contributions of different signalling pathways linked to these receptors to the various cellular responses (growth, maturation, functional activation) are not understood. In this project we aim to use cell and molecular biolo ....Growth factors acting on cell surface receptors activate multiple intracellular signalling pathways that regulate cellular growth and function. Mutations in the genes that code for these receptors or their downstream signalling pathways contribute to many human cancers. The contributions of different signalling pathways linked to these receptors to the various cellular responses (growth, maturation, functional activation) are not understood. In this project we aim to use cell and molecular biology approaches to determine the role of different signalling pathways in cellular responses mediated by the growth factor receptor c-Kit. The c-Kit receptor has essential functions in blood cell development, skin and hair pigmentation, gut function and the reproductive system. It is also essential for the development and function of mast cells which trigger allergic responses such as asthma and eczema. Mutant forms of the receptor have been identified in certain leukaemias and colon cancers. Many new drugs that target specific intracellular signalling pathways have recently been developed and are beginning to be evaluated in clinical trials. Better understanding of how individual pathways contribute to the function of c-Kit and other receptors is essential for optimal use of these new drugs. For example, it may enable the choice of drugs to block c-Kit dependent cancer cell growth or allergic reactions without affecting the growth of normal blood cells.Read moreRead less
Disorders of sexual development (DSDs) are surprisingly common, and often result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. In this Program we will pool our expertise in human molecular genetics, mouse developmental biology and protein chemistry to identify genes important for sex determination and development of the gonads, and discover how they contribute to DSD, in order to improve clinical care to patients with DSD.
Understanding And Preventing Adverse Developmental Effects Of Perinatal Infection/inflammation
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Exposure of babies to infection or inflammation within the womb is common and is associated with preterm delivery and illness in newborns. The biggest problem for these babies is lung disease due to inflammation of the lungs before birth and/or in response to lung injury after birth. We are investigating how inflammation alters lung development, and working on developing a novel cell therapy to prevent life-threatening newborn lung disease.
Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$4,580,898.00
Summary
Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo ....Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research program will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans. Australia boasts three of the foremost international researchers in sex determination. Their contributions have been fundamental to the advancement of the field, including the identification and characterization of the master testis determining gene and other genes critical for sex determination. They now propose to pool their expertise in human molecular genetics, mouse developmental biology and protein chemistry to bring spectacular advances in our knowledge of human sexual development and its associated disorders. This information will be used to bring improved clinical care to patients withdisorders of sexual development.Read moreRead less
Modern Chemical Exposures In Utero And In Infancy, And Their Impact Upon Early Neurodevelopmental Outcomes In The Barwon Infant Study, An Unselected Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$138,353.00
Summary
I am a paediatric doctor interested in the effects of modern industrial chemicals on children’s development. Even in the womb babies are exposed to industrial chemicals and we know some, like lead, are harmful to developing brains. I am interested in other chemicals that are now suspected to affect development, including the polybrominated diphenyl esters (PBDEs), and I intend to investigate this as part of the Barwon Infant Study, which follows 1250 children from before birth to 3 years.
Developing An In Vitro Model Of A Human Blastocyst
Funder
National Health and Medical Research Council
Funding Amount
$890,062.00
Summary
Using novel cellular and molecular technologies we propose to develop an artificial model of an early human blastocyst. This will allow us to study the first initial steps in human development without the use of real embryos. Such a model will not only help us decipher the first steps in human development, but we anticipate it will be essential to study how gene mutations and the environment affect this initial step in human development.