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.
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
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
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
Designer DNA-binding factors. This project aims to use a natural transcription factor family to enhance the efficiency and functionality of designer DNA-binding factors. Research into the structure and function of zinc finger transcription factors, TAL effectors and CRISPR created designer DNA-binding factors. However, though research has improved the specificity of these factors’ genome-wide binding, their efficacy in regulating the expression of genes requires improvement. Using sequencing, th ....Designer DNA-binding factors. This project aims to use a natural transcription factor family to enhance the efficiency and functionality of designer DNA-binding factors. Research into the structure and function of zinc finger transcription factors, TAL effectors and CRISPR created designer DNA-binding factors. However, though research has improved the specificity of these factors’ genome-wide binding, their efficacy in regulating the expression of genes requires improvement. Using sequencing, the project intends to enhance the efficiency and function of these factors by designing modules to improve the stability of DNA binding and effectiveness in functionally regulating gene expression. The project outcomes could include knowledge enabling the use of genetically engineered DNA-binding proteins to artificially control gene expression, with significant scientific and economic implications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101033
Funder
Australian Research Council
Funding Amount
$315,220.00
Summary
Genomic Diversity in the Human Brain: the Functional Role of Expandable DNA Repeats. Neuronal cells accumulate genetic changes during development and adult life, and recent evidence suggests that the resulting genomic diversity may underlie neuronal functional diversity. To date only a few types of somatic genetic variation have been characterised in the human brain. Trinucleotide repeats (TNR) are hotspots of genomic instability and TNR expansions at specific loci cause dozens of brain disorder ....Genomic Diversity in the Human Brain: the Functional Role of Expandable DNA Repeats. Neuronal cells accumulate genetic changes during development and adult life, and recent evidence suggests that the resulting genomic diversity may underlie neuronal functional diversity. To date only a few types of somatic genetic variation have been characterised in the human brain. Trinucleotide repeats (TNR) are hotspots of genomic instability and TNR expansions at specific loci cause dozens of brain disorders, suggesting that the human brain is particularly vulnerable to this type of genetic variation. This project aims to investigate, for the first time, TNR somatic instability in the human brain on a genome-wide scale, therefore, addressing the genetic diversity of the brain from a novel and highly relevant angle. Read moreRead less
The characterization of tiny Ribonucleic acids in animal epigenetics. Epigenetics, the inheritance of traits not encoded in deoxyribonucleic acid (DNA), is not well understood in animals. This project will investigate two classes of Ribonucleic acid (RNA) that may form part of an animal-specific epigenetic regulatory system. This study could revolutionize our understanding of animal genetics.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less