Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.
Dnmt3L Haploinsufficent Retrotransposition Leads To Genetic Hypermutation
Funder
National Health and Medical Research Council
Funding Amount
$613,982.00
Summary
This project aims to demonstrate the critical importance of DNA methylation as a cause of mutation and thus genetic diseases, many instances of sterility and low fertility, and cancers. Because DNA methylation can be partially determined by substrate availability, a demonstration of the importance of DNA methylation vis a vis mutation rates will refine our understanding of the impact of metabolism and nutrition on mutation rate as a cause of human disease.
Mechanistic And Functional Drivers Of Neochromosome Evolution
Funder
National Health and Medical Research Council
Funding Amount
$763,771.00
Summary
Neochromosomes are Frankenstein chromosomes--massive extra chromosomes that are stitched together from 100s of pieces of normal chromosomes. They are found in 3% of cancers, but are common in some types, such as liposarcoma. We have mapped their structure and found they form through punctuated chromosome shattering and gene amplification. We will investigate the precise molecular mechanisms that cause this and the recurrent transcriptional and epigenetic drivers lead to their formation.
Assessment Of Markers Of Genomic Instability For The Prediction Of Treatment Response In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$590,086.00
Summary
The success of therapy for patients with chronic myeloid leukaemia depends on close monitoring during therapy for early recognition of pending relapse, and the selection of appropriate treatment if drug resistance occurs. This project aims to identify patients at the start of therapy who are at risk of treatment failure by investigating their genetic profile. An increased frequency of gene mutations may indicate that patients require more aggressive therapy to achieve an optimal response.
Identifying Novel Genome Instability Signatures In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is the single biggest clinical problem facing the world. An underlying hallmark of cancer is the accumulation of errors in the genetic information of a cell which arises through genomic instability. This research project aims to investigate novel molecules identified by our screening that function in response to genomic instability in cancer. This study is expected to define roles for each molecule in the maintenance of genomic stability and predict for patient diagnosis and outcome.
Improving Treatment Of Non-small Cell Lung Cancer: Suppressing Cell Division Cycle Associated Protein 3 (CDCA3)
Funder
National Health and Medical Research Council
Funding Amount
$194,446.00
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide. This project will establish the worth of suppressing the molecule ‘cell division cycle associated protein 3’ (CDCA3) in lung cancer. To do so, we will adjust the levels of CDCA3 in animal lung cancer models and treat the tumours with chemotherapy and the novel drug CX-4945. We expect that reduced levels of CDCA3 combined with CX-4945 and/or chemotherapy in NSCLC patients will benefit patient outcome.
A Systems Biology Approach To Elucidate Common Principles And Mechanisms Underlying Triplet Repeat Expansion Associated Genetic Defects
Funder
National Health and Medical Research Council
Funding Amount
$1,033,615.00
Summary
Several human genetic diseases that affect the nervous system occur due to expansions of the DNA repeats in the genome. Here, we use a combination of cutting edge technologies such as systems biology and genomics to uncover the common principles and use them to devise novel therapeutic strategies.
Investigating Tumour Initiation And Growth In A Panel Of Mice Defective In Epigenetic Reprogramming.
Funder
National Health and Medical Research Council
Funding Amount
$421,600.00
Summary
Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatme ....Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatments in humans.Read moreRead less