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.
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
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
Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a ....Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a red blood cell line. Simultaneously, this project aims to generate fundamental insights into mechanisms of human gene regulation. The technological and biological outcomes of this project will be of benefit for future gene editing applications.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 .
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
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.