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.
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.
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.