A Fluorescent Zebrafish Model Of Endodermal Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
The most catastrophic event in cancer progression is when individual cancer cells move to other areas of the body and develop into secondary tumours. This very complex process shows striking similarities to cell movements during embryogenesis. In this project, we use a model system, the zebrafish, to analyse how cells move during embryogenesis. We will determine the genes required for cell movements in the zebrafish embryo, so we can find the corresponding genes in human cancers.
Regulation Of Innate Immunity And Tumour Progression By Activating Transcription Factor 3
Funder
National Health and Medical Research Council
Funding Amount
$473,469.00
Summary
Toll-like receptors (TLRs) play an essential role in innate immune responses and are involved in initiating tumourigenesis via inflammatory pathways. We have shown that the transcription factor ATF3 is a negative regulator of TLR signalling. We will study how modulation of the activity of ATF3 affects the inflammatory response and tumour progression. This will provide a molecular basis on which to design therapeutic reagents for the treatment of cancer.
Identification Of Breast And Ovarian Tumour Suppressor Genes On Chromosome 22 By Functional Complementation
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor ....Cancer is fundamentally a genetic disease that arises when errors (mutations) accumulate in genes involved in regulating how and when cells grow. An important class of gene involved in this process are the tumour suppressors whose primary function is to inhibit cell growth. It is widely believed that significant improvements in the treatment and diagnosis of cancer will only be achievable once we have a detailed understanding of how these genes work. It is likely that dozens of tumour suppressor genes exist in the human genome and of these only a small proportion have been identified. The aim of this study is to identify genes on human chromosome 22 that are involved in the development of breast and ovarian cancer. Genetic evidence from many investigators, including data from our own laboratory, has indicated that multiple tumour suppressor genes are present on human chromosome 22 but as yet none have been positively identified. Part of the difficulty in identifying these genes is that cancer cells often have a lot of genetic damage and it is hard to distinguish the important changes from background genetic noise'. To circumvent this problem we are using a functional cloning approach which identifies tumour suppressor genes by their ability to inhibit the growth of cancers cells grown in culture in the laboratory. Genes that are identified in this way will be evaluated for the presence of genetic mutations in real human cancers which will give us a better idea of their true significance in tumour development. In addition to enhancing our understanding of the process tumour development this project may identify new targets for anti-cancer therapies.Read moreRead less
APC Mutation And The Initiation Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,267.00
Summary
Colorectal (or bowel) cancer is a major health problem in Australia. At present it is the most common cancer, approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for advanced colorectal cancer are not very effective. Mortality from colorectal cancer is high, being second only to lung cancer as the leading cause of cancer death in Australia. ....Colorectal (or bowel) cancer is a major health problem in Australia. At present it is the most common cancer, approximately 1 in 21 Australians will develop the disease in his-her lifetime. The risk of bowel cancer increases with age, with the risk rising progressively and sharply from the age of 50. Current therapies for advanced colorectal cancer are not very effective. Mortality from colorectal cancer is high, being second only to lung cancer as the leading cause of cancer death in Australia. The development of colorectal cancer is affected by both genetic and environmental factors. Colorectal cancer progresses through a number of distinct pathological stages. This is thought to be the result of the progressive aquisition of mutations in genes that normally ensure a balance between cell growth and cell death. Mutations in a gene known as APC are associated with the very early stages of tumour formation in at least 80% of colorectal tumours. Our research is aimed at understanding how alterations in APC influence the behaviour and growth of colonic cells. We have developed a novel system where normal mouse colon can be maintained and grown for up to 2 weeks in a Petri dish. Alterations in the APC gene and other colon cancer genes will be introduced into the normal epithelial cell lining and the effects on the growth and behaviour of the cells in organ culture will be analysed. Our hypothesis is that changes in the APC gene affects the way cells migrate, divide and move. This work should improve our knowledge of the cellular changes that occur during tumour initiation in the bowel and aims to contribute to the design of new therapies for early intervention in colon cancer.Read moreRead less
Bombesin Like Peptides As Autocrine Growth Factors In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now kn ....Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. Colorectal carcinomas in common with other cancer types such as cancer of the prostate and lung often produce its own growth factors and receptors. Activation of the receptor by the growth factor further stimulates the tumour's growth and spread throughout the body. The objective of this project is to determine the potential roles of a growth factor termed Bombesin Like Peptide. This peptide, now known as GRP in mammalian systems, is an established growth factor in certain lung cancers but little is known about its role in tumours of the large bowel. We will study the expression and production of GRP and its receptors at the gene and protein level, the ability of GRP to stimulate growth, the chemical structures of GRP, and the potential of antagonists of GRP to modulate growth. Studies will be performed in patients with bowel cancer, in animal models of bowel cancer, and with bowel tumours removed from patients and bowel cancer cell lines. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as GRP receptor antagonists and radiolabelled GRP analogues for radiotherapy.Read moreRead less
Regulation Of Gastric Tumour Invasion And Growth By Gp130 Activating Cytokines.
Funder
National Health and Medical Research Council
Funding Amount
$625,642.00
Summary
Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . A ....Gastric cancer is a major cause of morbidity and death worldwide. We have previously established a very informative animal model of this disease which has facilitated a new understanding of the diverse role of the IL-6 family of cytokines in regulating gastric tumour growth and dissemination to distant organs. This proposal will focus on how the main members of this cytokine family, namely IL-6 and IL-11, inhibit gastric tumour invasion to other organs, and promote tumour growth respectively . An understanding of these processes will aid in designing therapeutic interventions specific for each cytokine and which may lead to drugs aimed at limiting or reversing this disease.Read moreRead less
Induction Of Senescence In Cells That Use The Alternative Lengthening Of Telomeres (ALT) Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$474,048.00
Summary
Approximately 10-15% of all cancers depend on Alternative Lengthening of Telomeres (ALT) for their continuing growth. A key aspect of many successful cancer treatments is that they force cancer cells to undergo a form of permanent growth arrest called senescence. In this study we will investigate characteristics of ALT-positive cancer cells that may make them especially vulnerable to senescence. This may be exploited in the future as a therapeutic strategy for cancers that depend on ALT.
The Tumour Suppressor Lgl In The Regulation Of Cell Signaling, Proliferation And Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$534,871.00
Summary
Cancer is a disease that affects 1-3 people at some point in their lifetime. Therefore, understanding what causes cancer is of major importance to medical science. This proposal focuses on a group of tumour suppressors, Scrib-Dlg-Lgl, which act in a common pathway to regulate cell polarity (cell shape) and proliferation. We have shown that Lgl also regulates cell death. This proposal focuses on understanding the mechanism by which Lgl regulates the cell proliferation and death machinery.
The Role Of Snail Family Proteins In Stem Cells And Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
This project investigates the role of a family of genes in regulating stem cells in normal tissues and cancer. This family can switch other genes off and we hypothesize that keeping these genes off is required to allow stem cells to be maintained in tissues. We combine novel studies in fruit flies and mice to examine gene function in stem cells and tumour initiation. These studies will increase our knowledge of how to manipulate stem cells and may identify new targets for tumour therapy.