Analysis Of Very Early Cancer-related Methylation Abnomalities
Funder
National Health and Medical Research Council
Funding Amount
$422,310.00
Summary
The factors that are involved in triggering cancer are still unknown. Increasing evidence however indicates that the DNA in the pre-cancer cell becomes modified leading to altered expression of important genes called tumour suppressor genes. Often the DNA is deleted or mutated but it can also become chemically changed by a process called DNA methylation. We have found that an important tumour suppressor gene called p16 is inactivated and chemically methylated in breast epithelial cells at the st ....The factors that are involved in triggering cancer are still unknown. Increasing evidence however indicates that the DNA in the pre-cancer cell becomes modified leading to altered expression of important genes called tumour suppressor genes. Often the DNA is deleted or mutated but it can also become chemically changed by a process called DNA methylation. We have found that an important tumour suppressor gene called p16 is inactivated and chemically methylated in breast epithelial cells at the stage when the cell changes to a pre-cancer cell. This grant is aimed at finding what triggers the silencing and methylation of the p16 gene in this early pre-cancer stage. We also plan to identify other genes are methylated and undergo inactivation the pre-cancer breast cells. These results will have an impact on understanding the molecular mechanism that makes a breast cell susceptible to cancer and may lead to insights into new prevention and treatment strategies.Read moreRead less
A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
Identification Of Critical Regulatory Elements In The BRCA1 Gene
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of the ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of these genes makes. This is largely due to limitations in current mutation detection strategies and an incomplete understanding of all of the genetic elements for which disruption can lead to loss of gene function. This propsal aims to identify all of the genetic elements critical for the expression of an important breast cancer gene called BRCA1. Furthermore, it aims to determine the status of these elements in breast cancer patients, thus expanding our knowledge of the actual contribution disruption of this gene makes to this disease.Read moreRead less
Investigation Of The Anticancer Action And Cytotoxic-synergism Of Matrix Metalloproteinase Inhibition.
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely ....In virtually all cases, death from solid tumors (including breast cancer) results from invasion and metastasis. The exciting recent pre-clinical observations that a new class of anticancer agents (which primarily target tumour invasion and metastasis) operate synergistically with a number of standard chemotherapy cytotoxics (such as those already used to treat breast cancer) suggests a new and significant additional therapeutic potential for both agents. The basis of this synergism is completely unknown however, and it is our contention that this mechanism needs to be explored at the molecular level in order to identify which combinations will have most potential in the clinic. This proposal aims to characterize synergistic combinations in an animal model of breast cancer progression, and to determine the specific molecular mechanism of the process. Each phase of the proposed study is a worthwhile undertaking in itself, and while it makes primary use of a breast cancer growth and metastasis system, the information revealed should be relevant to many tumour types. This information can be used to formulate new therapeutic strategies for the treatment of solid tumours and their metastasis in patients.Read moreRead less
This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does ....This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does not achieve this through changing genetics the library always stays intact. Rather, it acts by using proteins or chemicals to make DNA functional in one way, or another. Genomic imprinting is a special type of epigenetics. While an embryo has received identical genetic information from each of its parents, the epigenetic information received from each parent was not entirely the same. Some genes which behave differently according to what parent they came from. For example, a gene that makes a growth factor protein is active only if received from the father. If received from the mother, it is inactive, and makes no protein. Genes behaving in this way are known as imprinted genes. We are trying to discover what epigenetic mechanisms are behind this behaviour of imprinted genes. One way we are approaching this problem is to study germ cells the cells giving rise to eggs and sperm. These cells are unusual in that their imprinted genes behave in the same way regardless of whether they were received from the mother or father, i.e., like any other gene. If we can understand why this is the case, we will be better able to understand why imprinted genes behave the way they do in the rest of the cells of the body. Broadly, the mechanisms we uncover should further our understanding of germ cell development, gene expression, and disease. Perturbations in the epigenetic profile are likely causes of human disease, including cancer.Read moreRead less
Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the ....Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the most fundamental questions in the whole of biology: what is the basis for the primal distinction between sex and soma?Read moreRead less
How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. ....How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. This research will continue Australia's high profile in reproductive biology using one of our iconic native mammals. A greater understanding of marsupial reproduction will also contribute to management of our threatened marsupial populations.Read moreRead less