Use Of Circulating Tumour DNA To Characterise The Mutational Landscape Of Marginal Zone Lymphoma, Monitor Treatment Response And Detect Emergence Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Marginal zone lymphoma (MZL) is a subtype of B-cell non-Hodgkin lymphoma for which the molecular drivers of disease are poorly understood. We hypothesise that circulating tumour DNA may be ideal for characterising the genetic mutations that underpin MZL, monitoring treatment response and detecting emergence of resistance. This non-invasive method of disease monitoring has the potential to transform management of cancers such as MZL, identify new treatment options and improve survival outcomes.
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.
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
In melanoma we hypothesise there is a series of as yet unidentified gene fusions which provide oncogenic stimulatory signals that promote tumour growth and that these novel fusion products are excellent targets for the design of new therapies to treat melanoma. The aims of this study are to identify oncogenic fusions in melanoma, to assess which of these are recurrent, and to demonstrate that the resulting fusion proteins provide a selective growth and-or survival advantage to the tumour cell.
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.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
Defining Biomarkers Of Colorectal Cancer Prevention By Dietary Agents And Translation To Human Intervention Studies
Funder
National Health and Medical Research Council
Funding Amount
$632,924.00
Summary
This research will explore dietary agents for their ability to regulate the damage to DNA that is responsible for causing bowel cancer. The plan is to identify a dietary approach that will effectively reduce the risk of colon cancer. The science will be tested in animal models followed by initial human experiments aimed at testing the relevance to humans.
It is seldom the initial cancer that kills the patient; most deaths are due to its metastatic spread throughout the body. Survival after the onset of a brain metastasis is dismal. Current understanding of cancer spread to the brain is poor and yet an ability to inhibit this process would save thousands of lives each year. Using rare tissue resources and cutting-edge technologies, this project will elucidate molecular features of brain metastases that can be exploited to generate new treatments.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.