Most normal cells naturally cease their growth because their chromosomes erode from repeated cell division. The erosion takes place at the ends of the chromosomes, or telomeres. All cancer cells avoid this erosion, and thus fail to cease their growth. About 85% of all cancers achieve this by activating an enzyme called telomerase, an enzyme that allows cancer cells to avoid the natural ageing process. This project aims to understand how this enzyme gets recruited to chromosome ends.
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.
Molecular Regulation Of Replicative Lifespan; Implications In Carcinogenesis And Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
The lifespan of normal cells in the body is limited by the number of times they can replicate. In contrast, cancer cells can replicate indefinitely – they are immortal. Our proposed investigations will determine how the mechanisms that control cell lifespan become dysfunctional as normal cells evolve into cancer cells. Understanding these mechanisms will enable the development of new anti-cancer drugs that will reverse cell immortality and halt the replication of cancer cells.
Epigenetic Regulation Of Telomere Chromatin And Genome Stability
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Telomeres are structures at the end of the chromosomes that impact cell replication. 15% of cancers, called ALT cancers, show telomere instability, increased DNA damage and are frequently mutated for the ATRX gene. ALT cancers have poor prognosis, due to the limited understanding of ALT cancer activation. This study aims to create a model of ALT activation to uncover the mechanisms that control ALT tumourigenesis. This could lead to potential ALT-specific diagnostic and therapeutic tools.
Function Of ATRX, H3.3 And PML Nuclear Bodies In The Regulation Of Telomere Chromatin Integrity
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual tel ....The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual telomere renewal in ES cells.Read moreRead less
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
Sleep, Telomere Length And Cardiorespiratory Phenotype In 11-12 Year Old Children: Cross-sectional Australian National Population Based Study
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
Telomeres are special areas at the ends of our chromosomes that ‘protect’ our DNA as our body cells divide. With ageing, our telomeres slowly become shorter, but the rate at which this happens varies. My project will investigate the associations between poor sleep duration and quality, increased risk of cardiovascular diseases, poor respiratory health and increased vulnerability to viral infections to shorter telomere length.