Normal healthy cells reproduce themselves with a remarkable fidelity. This ensures the stable inheritance of our genetic material, or DNA, and is essential for normal tissue development and maintenance. Cancer cells, on the contrary, show a high degree of rearrangements to their chromosomes, the bodies that hold the DNA. This is a result of a process known as genomic instability. This instability allows normal cells to become cancerous through the accumulation of a number of genetic changes. Thi ....Normal healthy cells reproduce themselves with a remarkable fidelity. This ensures the stable inheritance of our genetic material, or DNA, and is essential for normal tissue development and maintenance. Cancer cells, on the contrary, show a high degree of rearrangements to their chromosomes, the bodies that hold the DNA. This is a result of a process known as genomic instability. This instability allows normal cells to become cancerous through the accumulation of a number of genetic changes. This project looks at a biochemical pathway, called the G2 DNA damage checkpoint, which functions in cells to prevent cell division when the chromosomes have been damaged. Once they have been repaired, this brake is relieved, and the cells will then divide without genetic alterations. We are concentrating our studies on an enzyme, called chk1, which is the final point of this pathway. Chk1 biochemically modifies the proteins that control cell division, and stops them from carrying out their normal function when the chromosomes are damaged. Our work will determine how chk1 is told by the cell to carry out this function, and how failure to do so leads to cancer.Read moreRead less
The Melanoma Susceptibility Gene Product P16 Functions In A UV-induced Cell Cycle Checkpoint In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$204,131.00
Summary
The contribution of the ultraviolet component of sunlight to skin cancer generally, and melanoma in particular, is widely acknowledged. However, the actual mechanism by which ultraviolet radiation changes the normal skin melanocytes, the pigmented skin cells, into cancerous melanomas is unclear. Several years ago, a gene was identified that was found to be mutated in a high proportion of sporadic melanomas, and was also found to be mutated in a proportion of families with a predisposition to dev ....The contribution of the ultraviolet component of sunlight to skin cancer generally, and melanoma in particular, is widely acknowledged. However, the actual mechanism by which ultraviolet radiation changes the normal skin melanocytes, the pigmented skin cells, into cancerous melanomas is unclear. Several years ago, a gene was identified that was found to be mutated in a high proportion of sporadic melanomas, and was also found to be mutated in a proportion of families with a predisposition to developing melanoma. This melanoma susceptibility gene, p16, can act to block cells growth, thus loss of this gene function in disease could lead to uncontrolled cell growth, a hallmark of cancer. This proposal investiagtes the role of p16 in responses of normal skin cells to ultraviolet radiation. We will examine the increased levels of p16 detected in skin after exposure to low doses of ultraviolet radiation and attempt to define the growth responses of these cells to the increased p16 levels. This project will help to establish the normal role of p16 in cellular responses to ultraviolet radiation, and may also identify novel targets for diagnosis, prevention or treatment of melanoma.Read moreRead less
G2 Phase Cdk2/cyclin A Co-ordinates Multiple Pathways In G2/M Progression
Funder
National Health and Medical Research Council
Funding Amount
$302,036.00
Summary
Cell growth is a tightly regulated process that ensures the exact duplication of the entire genomic DNA followed by division of the cell into two identical daughter cells. If this strict ordering of events is in any way disrupted, the resultant daughter cells would have a different complement of DNA from their parent cell, essentially mutant cells. The cell has established a mechanism to ensure the correct ordering of these crucial events, known as the cell cycle, and mechanisms that can respond ....Cell growth is a tightly regulated process that ensures the exact duplication of the entire genomic DNA followed by division of the cell into two identical daughter cells. If this strict ordering of events is in any way disrupted, the resultant daughter cells would have a different complement of DNA from their parent cell, essentially mutant cells. The cell has established a mechanism to ensure the correct ordering of these crucial events, known as the cell cycle, and mechanisms that can respond to disruptions in this ordering and halt the normal cell cycle mechanism until the fault is rectified. These are the checkpoint controls. Checkpoint controls also respond to environmental stresses such as toxins that can damage the DNA to produce mutations. In diseases such as cancer, these checkpoint mechanisms are often faulty, allowing the cells to accumulate DNA mutations which can ultimately result in the cells becoming the aggresive, malignant tumours associated with the worst forms of this disease. Thus a detailed understanding of the cellular mechanisms involved in normal cell cycle and checkpoint control is important in not only defining the causes of these diseases at a molecular level, but may ultimately provide molecular targets for drugs that specifically destroy cancer cells by targeting the faulty checkpoint control. This proposal will investigate one component of the cell cycle mechanism, cdk2-cyclin A, which also has a major role in checkpoint control, to determine its exact role in both these important cellular growth controls.Read moreRead less
I am a molecular and cellular biologist with particular interest in understanding the regulation of DNA damage surveillance pathway and its role in the maintenance of genome stability.
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Examining The Importance Of DNA Damage Repair For Oocyte Quality, Female Fertility And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Application Of New Technologies And Methods In Nutrition Research – The Example Of Phenotypic Flexibility
Funder
National Health and Medical Research Council
Funding Amount
$210,823.00
Summary
The aim of the Nutritech project is to develop better diagnostics of the effect of foods and dietary supplements on the health of an individual. NutriTech will develop new analytical technologies to comprehensively investigate the diet-health interrelationship and critically assess their usefulness for the future of nutrition research. A new automated method for measuring the effect of diet on multiple measures of DNA damage and nutrients in single cells will be developed at CSIRO.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.