A Novel Mechanism For Sustained Proliferation Of Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$565,881.00
Summary
We have found that some tumours use a previously unknown strategy for evading the normal limits on cellular proliferation. We will analyse the molecular details of this mechanism in order to (i) understand how it works, (ii) devise a diagnostic test, and (iii) lay the foundations for developing treatments that specifically target this type of cancer.
Title: Mechanisms of telomere cap function DNA within each cell is packaged into chromosomes, the ends of which are called telomeres. The DNA in telomeres consists of 6 letters of the genetic code, TTAGGG, repeated hundreds or thousands of times. A number of proteins, including some that have not yet been identified, bind to this DNA and form a cap structure to protect the chromosome ends. Telomeres need to be able to serve a number of specialised functions, including protection against enzymes ....Title: Mechanisms of telomere cap function DNA within each cell is packaged into chromosomes, the ends of which are called telomeres. The DNA in telomeres consists of 6 letters of the genetic code, TTAGGG, repeated hundreds or thousands of times. A number of proteins, including some that have not yet been identified, bind to this DNA and form a cap structure to protect the chromosome ends. Telomeres need to be able to serve a number of specialised functions, including protection against enzymes that degrade DNA ends, and preventing chromosome ends from sticking to each other, while allowing access for DNA copying enzymes when the cell is preparing to divide into two. In some inherited conditions, the telomeres fail to perform these functions efficiently, leading to cellular dysfunction, premature ageing of cells, and ultimately disease. In some types of cells, especially cancer cells, the telomeres also permit the access of molecular machinery that lengthens the telomeres. There are at least two types of lengthening processes, one of which is a complex enzyme called telomerase, and the other an incompletely characterised process that we discovered and named Alternative Lengthening of Telomeres (ALT). In some circumstances, the telomeres of cancer cells appear to be able to discriminate between telomerase and ALT, and to allow one mechanism to operate but not the other. We will analyse how telomeres perform their capping functions, and will determine the differences between normal and cancer cells in this regard. This will lay the groundwork for efforts to develop new forms of cancer treatment that act by preventing cancer cells from lengthening their telomeres.Read moreRead less
Progenitor Origin And Regulation In Endometrial Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$847,583.00
Summary
The endometrium is the lining of the uterus and regenerates each month during a woman's reproductive years. Stem and progenitor cells in the endometrium are thought to be responsible for this regeneration. We have identified a genetic marker for stem and progenitor cells in the endometrium of mice and will use this to understand endometrial regeneration. This work will address infertility as well as overactive endometrial growth in diseases such as endometriosis and endometrial cancer.