Molecular Mechanisms And Control Of Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$453,055.00
Summary
Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell fr ....Studies of a mechanism cancer cells use to protect the ends of their chromosomes The DNA within cell nuclei is arranged in linear packages referred to as chromosomes, capped at each end by structures called telomeres. Telomeres consist of a long stretch of a repetitive DNA sequence that does not contain any genes. Most normal cells are unable to copy the DNA at the extreme ends of their chromosomes, so every time they divide their telomeres get slightly shorter. This ultimately stops the cell from dividing any further, and acts as a very potent barrier to the cell becoming cancerous. Some normal cells are not subject to this inexorable telomere shortening: these are the germ cells in the testis and ovary, that are responsible for passing on genetic material to the next generation. Such cells express an enzyme, telomerase, which is able to synthesise new telomeric DNA to replace that lost during cell division. 85% of human cancers are also able to prevent shortening of their telomeres - and thus have breached the barrier that normally prevents unlimited cell proliferation - via telomerase activity. Therefore, if drugs that inhibit telomerase can be developed they may be a very useful new form of cancer treatment. We have found, however, that some cancers are able to prevent telomere shortening by a process that does not involve telomerase, and which we refer to as Alternative Lengthening of Telomeres (ALT). One practical implication of this finding for the design of new cancer treatments is that telomerase inhibitors will need to be used in combination with ALT inhibitors. In this study, we will determine A. how normal cells keep the ALT mechanism permanently shut down and B. the molecular details of the ALT mechanism itself. An understanding of these processes may ultimately contribute to the development of novel cancer treatments that disrupt the ability of cancer cells to divide an unlimited number of times.Read moreRead less
Definition Of The Role Of Senescence In Tumour-associated Endothelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$583,081.00
Summary
'Cellular senescence' is a mechanism to stop cells growing, and it may protect against tumour growth. However, it may also induce changes in cells leading to 'pro-tumour' effects. We have identified a gene - which we have called SEN1 - which induces senescence in the blood vessels of tumours. This gene may cause alterations in the blood supply to the tumour allowing it to grow and to resist chemotherapy. Understanding this gene may allow us to treat cancer by shutting off its blood supply.
Defining The Role Of Wnt Signaling In Hepatocellular Carcinoma And The Potential Of Wnt-targeted Therapy For HCC
Funder
National Health and Medical Research Council
Funding Amount
$403,210.00
Summary
Of all cancers, liver cancer is the third biggest killer worldwide and there is currently no effective treatment options for this disease. We now know many of the common genetic changes that occur in liver tumour cells but have yet to develop targeted drug treatments. This project is aimed at determining whether reactivating a tumour cell's normal cancer suppressing functions can stop tumour growth and whether we can use this information to develop specific drugs that target liver tumour cells
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.
Ataxia-Telangiectasia: An Emerging Role For Inflammation In Driving Neurodegeneration And Premature Ageing
Funder
National Health and Medical Research Council
Funding Amount
$437,436.00
Summary
Ataxia-Telangiectasia (A-T) is a devastating genetic disease that arises in early childhood and causes patients to die in their twenties. To date there is no cure, and therapeutics are desperately needed. This project will use state-of-the-art brain organoids derived from stem cells of A-T patients in order to better understand this disease and evaluate novel drugs that target the molecular mechanisms that drive chronic inflammation and brain neurodegeneration in children with A-T.