Ubiquitin And SUMO DNA Damage Response Signalling At Deprotected Telomeres During The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Following genome damage cells stop the cell division process and initiate DNA repair. We discovered that at specific times during cell division his does not happen if the damage signals originate from the chromosome ends (i.e. “telomeres”). We anticipate this is necessary to prevent genomic instability in healthy cells and may be driving genomic instability in cancer cells. Experiments described here will elucidate the molecular mechanisms and biological significance of our observation.
Targeting Chromosomal Instability By Metabolic Stress
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
The most intractable cancers gain and lose DNA as they grow, making them highly variable and drug resistant. We have found that mild disruptions to their use of energy can specifically kill cells with this kind of genetic instability. In this project we will characterize the mechanism by which metabolic stress affects cell division and the survival of genetically unstable cells. Our objective is to find treatments with no effects on normal cells that eliminate unstably dividing cancer cells.
The Control And Regulatory Mechanisms Of Artemisinin Induced Dormancy In P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$495,552.00
Summary
Malaria is a major global health problem and can only be reliably treated with artemisinin combinations in many areas due to widespread of drug resistance. However a proportion of parasites appear to be able to avoid the lethal effects of the drug by becoming “dormant” following exposure. They resume growth after the drug is wanned, a feature which is reminisent to cell cycle arrest. This study investigates the role of cell cycle machinery in dormancy following arteminsinin treatment.
Elucidating The Tumour Suppressor Behaviour Of FUBP1 In Glioma
Funder
National Health and Medical Research Council
Funding Amount
$940,780.00
Summary
Treatment strategies for patients with invasive brain tumours are based on a WHO tumour grading system. This system does not account for differences within tumour types, although these can significantly affect treatment outcomes. This project aims to investigate new drug therapies for specific brain tumour types, and to identify new prognostic markers for these tumours. These studies will lead to more individualised treatments, which is critical to improving patient survival and quality of life.
Developing Cancer Therapies That Target Chromosomal Instability
Funder
National Health and Medical Research Council
Funding Amount
$644,126.00
Summary
A significant reason why late-stage cancers are hard to treat with drugs is because the tumour cells show genetic variability, always producing new variants that sooner or later get around the drugs. We intend to combat this by targeting the ability of cancer cells to vary genetically - we are discovering ways to specifically kill genetically unstable cells. This prevents the cancer from developing drug resistance as well as having less side effects on the patient's normal cells.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
Understanding How Defects In Chromosome Structure Can Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$546,557.00
Summary
The correct folding of DNA is critical to a cell's survival. This is orchestrated by a special class of proteins called the condensins. Defects in condensin lead to aberrant chromosome folding and disease. We aim to understand how condensin folds chromosomes and why mutations in condensin are increasingly associated with disease.
Understanding The Biological Regulation Of MLKL And Its Role In Necroptotic Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$656,979.00
Summary
Cell death is a normal process that permits the growth and defence of our vital tissues. One kind of cell death, necroptosis, is characterized by the swelling and bursting of cells. When cells ‘explode’ in this uncontrolled way they provoke an inflammatory response. This may be a factor behind illnesses ranging from colitis to cardiovascular disease. Understanding necroptotic cell death may pave the way for new therapies for those that suffer from these devastating conditions.
Understanding The Structure And Function Of The Chromosome Condensin Complex
Funder
National Health and Medical Research Council
Funding Amount
$620,731.00
Summary
In order to survive cells need to divide their genetic material (DNA) equally between two daughter cells. For correct cell division to occur DNA has to be correctly packaged into condensed and organised chromosomes. Improper packaging of genetic material can result in unregulated cells that may become cancerous or lead to other genetic diseases such as Down's Syndrome. Understanding the key players regulating this process is vital to allowing researchers to further work in these areas.
Real Time Visualisation Of T Cell Cycling During Influenza Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$589,679.00
Summary
Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of an ....Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of anti-viral immunity and immuno-senescence.Read moreRead less