Interaction Of TRF2 With DNA Repair Proteins In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$297,246.00
Summary
10-15% of human cancers, including some of the most difficult-to-treat and aggressive, depend for their continuing growth on a molecular process called Alternative Lengthening of Telomeres (ALT). We have identified for the first time a protein whose normal role includes repressing ALT. We will study how this protein works, what its molecular partners are, and how these molecules interact with each other. This information is expected to lay the foundations for cancer treatments that target ALT.
Understanding The Function Of Recql4 In DNA Replication And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
We are interested in understanding how cancer forms. We are using information from human cancers to understand how a protein causes cancer. We are using models to understand how mutations in this protein give rise to bone cancer. These models are used together with detailed biochemistry to understand how the mutations affect protein function.
Understanding The Role Of SSB1 In Embryonic Development And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Normally DNA exists as a double helix where two strands are zipped together. When single-stranded (ss) DNA is exposed during various cellular processes it can be easily damaged and degraded by cellular enzymes, but is protected by ssDNA binding proteins (SSBs). We have identified two new SSBs (SSB1 and SSB2) that play a crucial role in DNA repair and will investigate the role and physiological function of these important proteins.
Understanding the mechanisms in the development of mutations in cancers will assist in development of targeted therapies to overcome chemotherapy resistance. The recently discovered TMPRSS2:ERG fusion in prostate cancer is unique as dominant fusion translocations are uncommon in solid organ malignancy. Activation induced cytidine deaminase (AID) is thought to play a role. Understanding the role of AID and downstream DNA repair pathways may be a target for future therapies in cancer.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Translating Molecular Determinants Of Susceptibility And Progression In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$6,510,085.00
Summary
Breast cancer is the most common cancer in women. Despite improvements in prevention, detection and treatment, it is the 2nd most common cause of cancer death in Australian women. Research advances in the last decade have improved our understanding of the pathways from susceptibility to progression and metastasis but this has mostly not yet translated into better outcomes. This program aims to translate some of our fundamental discoveries to improve outcome for affected women and their families.
Identifying The Mechanism Of The G2 Phase UV Checkpoint And Repair Response Commonly Defective In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$569,656.00
Summary
The UV component of sunlight is the major environmental factor driving the development of melanoma. UV radiation can directly mutate genes resulting in their inability to perform normal functions which may contribute to cancer. Despite the high number of mutations directly attributable to UV radiation, the mechanisms known to repair these mutations are generally normal in melanoma. This research will investigate a repair mechanism we have identified that is commonly defective in melanomas.
Synthetic Lethality Screen Targeting A Defective Checkpoint In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$552,121.00
Summary
All cancers have defects in the mechanisms that regulate normal cell growth and division. These defects provide a growth advantage for the cancer, but can also be an Achilles Heel. In this project we will investigate targeting a defective control mechanism we found in a high proportion of melanomas. We will identify genes that when inhibited combine with the defective control to specifically kill tumour cells with this defect. Normal tissue is protected by its intact regulatory mechanism.
Structural And Biochemical Investigation Of The Bloom�s Complex, Defective In Bloom�s Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$184,661.00
Summary
Bloom�s Syndrome is a rare inherited disorder that results in greater than 90% risk of developing cancer by the age of 25. The gene that causes Bloom�s Syndrome, called BLM, protects cells from cancer-causing mutations hence affected individuals develop the same types of cancers as the general population, only much faster. We will investigate the properties of the BLM gene product and understand how it protects us from cancer, and may influence some forms of cancer treatment.