Mechanistic And Functional Analysis Of The Id4 Proto-oncogene In Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$693,983.00
Summary
Cancer arises through damage to normal regulatory processes in cells. Understanding these damaged processes is essential to implement personalized medicine. This proposal explores the role of the proto-oncogene ID4 in the closely related cancers triple negative breast cancer and serous ovarian cancer. This research may lead to the development of new therapeutic strategies or the refinement of existing strategies for these poor prognosis cancers.
Ubiquitin And SUMO DNA Damage Response Signalling At Deprotected Telomeres During The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Following genome damage cells stop the cell division process and initiate DNA repair. We discovered that at specific times during cell division his does not happen if the damage signals originate from the chromosome ends (i.e. “telomeres”). We anticipate this is necessary to prevent genomic instability in healthy cells and may be driving genomic instability in cancer cells. Experiments described here will elucidate the molecular mechanisms and biological significance of our observation.
Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways m ....Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways may lead to a novel methodology to activate silenced genes as well as determine the role of ncRNAs in genome evolution.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100199
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Determining the mechanisms of transgenerational epigenetic inheritance. Although previously controversial, there is now little doubt that transgenerational inheritance of epigenetic marks can occur. This phenomenon is difficult to study in humans and many model organisms, in part due to long generation times. To avoid this difficulty, this project will use genetic and molecular biology approaches in the model organism Caenorhabditis. elegans. The project will utilise a robust assay for transgene ....Determining the mechanisms of transgenerational epigenetic inheritance. Although previously controversial, there is now little doubt that transgenerational inheritance of epigenetic marks can occur. This phenomenon is difficult to study in humans and many model organisms, in part due to long generation times. To avoid this difficulty, this project will use genetic and molecular biology approaches in the model organism Caenorhabditis. elegans. The project will utilise a robust assay for transgenerational epigenetic inheritance established to identify a collection of genes involved in the process and will determine the interplay between chromatin modifications and small RNA molecules. This project aims to determine the exact epigenetic mark that is transmitted and the mechanisms by which the transmission occurs.Read moreRead less
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
The Contribution Of Subunit Interfaces To Receptor Activation In Ligand Gated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$309,070.00
Summary
This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors ....This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors in the brain and how they can be modulated.Read moreRead less