Regulation Of The Quality Of DNA Repair By Timing In The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$468,794.00
Summary
During responses to infection or immunisation, antibody-producing _B� cells mutate their antibody genes at extreme rates. Rare mutations which improve the antibodies are selected by competition between B cells favouring those which make the best antibodies: Darwinian evolution on extreme _fast-forward�. We aim to understand this process because it is essential for normal immunity and effective vaccination, and because when it goes wrong, it can cause aggressive human cancers.
A Tumour Suppressor Pathway That Removes DNA-RNA Hybrids
Funder
National Health and Medical Research Council
Funding Amount
$935,780.00
Summary
DNA:RNA hybrids are found normally in our chromosomes. But, the regions where DNA:RNA hybrids form are linked to chromosome changes that occur during breast and blood cancer development. We have uncovered why these chromosome changes occur, and have linked it to the important function of a cancer-associated gene called FANCM. Our study is exploring this important finding that has implications for both the cause and treatment of cancer.
Biochemical Reconstitution Of The Ubiquitin Ligase Pathway Defective In Fanconi Anaemia
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Fanconi Anemia (FA) is characterised by loss of vital blood cells but also 700x risk of developing leukaemia and other cancers. FA is caused by an inherited defect in one of 15 different genes that provide a signal and repair mechanism protecting cells from cancer causing mutations. By reconstructing this signaling mechanism in the test tube we will determine how it contributes to cancer protection, and highlight potential strategies for treatment of FA and leukaemia in the general population.
Multi-domain Regulation Of DNA Damage Response Kinases
Funder
National Health and Medical Research Council
Funding Amount
$313,427.00
Summary
DNA damage plays a key role in the onset of cancer and the response to cancer therapies. Mutations in the Chk2 DNA damage response kinase are associated with increased cancer risk. We will study detailed mechanisms how phosphorylation of Chk2-like kinases contributes to normal copying of our DNA every time a cell divides, and how it regulates how Chk2 is activated. The studies will improve our understanding how cancer may originate and how cancer cells respond to chemo- or radiation therapy.
Biochemical Investigation Of Ubiquitination By The Fanconi Anaemia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$603,447.00
Summary
Fanconi anaemia is an inherited disorder with greatly elevated risk of leukaemia and cancers. The causal genes are ‘tumour suppressors’ that protect us from cancer by a complex function in repair of damage to our DNA. This study aims to understand how this DNA repair function protects us from cancer, and may influence some forms of new forms of cancer treatment.
How is molecular information passed between generations? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will combine use of the model organism Caenorhabditis eleg ....How is molecular information passed between generations? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will combine use of the model organism Caenorhabditis elegans with biochemistry and structural biology to determine what the molecular mechanism is by which this "transgenerational epigenetic inheritance" occurs.Read moreRead less