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.
Fibroblast Senescence As A Driver Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$845,611.00
Summary
Idiopathic pulmonary fibrosis (IPF) has no cure. Currently we think that IPF develops like normal wound healing, but the normal “braking” mechanisms in the myofibroblasts (the cells that produce the connective tissue) don’t work, such that too much connective tissue is produced and oxygen transfer to the blood is stopped. We have identified a protein we think stops, the myofibroblasts from dying. Reducing the activation of this protein should return the myofibroblasts function to normal.
We have recently discovered that MOZ (monocytic leukaemia zinc finger gene), a gene first identified in rmutations leading to a particularly aggressive form of leukaemia, is a major regulator of senescence. In the absence of MOZ cells exit the cell cycle and become senescent, independently of DNA damage. These obsevations are very important for understanding cancer development because for cancer to grow and spread the cells must avoid senescence.
ALT-associated PML Bodies: Keys To The Biology And Treatment Of An Important Subset Of Cancers
Funder
National Health and Medical Research Council
Funding Amount
$813,614.00
Summary
Alternative Lengthening of Telomeres (ALT) is a molecular mechanism used by ~10% of cancers to sustain their relentless growth. ALT is common in sarcomas and brain tumours which are difficult to treat. ALT cancers contain nuclear structures called ALT-associated PML nuclear bodies (APBs) which may be part of the ALT machinery. This research will investigate characteristics of APBs and how they are formed, and will use this information to identify drugs to treat ALT tumours.
NAD+ And SIRT2 Regulation Of Mitotic Lifespan, Senescence And Healthy Ageing
Funder
National Health and Medical Research Council
Funding Amount
$617,274.00
Summary
During youth, cells in our body undergo a continual process of self-renewal, known as mitosis, where cells divide and accurately provide equal number of chromosomes into each daughter cell. During old age, dysfunctional mitosis leads to senescence, where cells no longer divide, and are unable to renew old tissue. We have uncovered a new molecular pathway involving the enzyme SIRT2 that maintains healthy mitosis, and will determine if targeting this pathway preserves health into old age, and ulti ....During youth, cells in our body undergo a continual process of self-renewal, known as mitosis, where cells divide and accurately provide equal number of chromosomes into each daughter cell. During old age, dysfunctional mitosis leads to senescence, where cells no longer divide, and are unable to renew old tissue. We have uncovered a new molecular pathway involving the enzyme SIRT2 that maintains healthy mitosis, and will determine if targeting this pathway preserves health into old age, and ultimately extends lifespanRead moreRead less
The Effect Of Selected Nutraceuticals On Brain Blood Vessels And Memory.
Funder
National Health and Medical Research Council
Funding Amount
$445,206.00
Summary
The human brain receives 1000L of blood per day, distributed through minute vessels called capillaries. The integrity and function of brain capillaries is compromised with aging and this may contribute to memory disturbances. Our laboratory has identified several naturally occurring compounds that prevent age-associated defects of brain capillaries. The primary aim of this project is to explore if these agents are beneficial for restoring brain capillary function and memory.
A Novel Approach To Restoration Of Tumour Suppression In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,604.00
Summary
Loss of a tumour suppressor is a key event in every cancer, including lung cancer. Therefore restoration of the expression and/or activity of the tumour suppressor is an attractive approach to anti-cancer treatment. In order to restore tumour suppression, a detailed understanding of the mechanism by which a given tumour suppressor is regulated is required. This application focuses on our discovery of a novel mechanism by which a key tumour suppressor of lung cancer is regulated.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.