Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Understanding The Regulation Of The Location Of Chromosomes Within The Nucleus
Funder
National Health and Medical Research Council
Funding Amount
$333,612.00
Summary
The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regio ....The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regions of the genome attach to the nuclear lamina.Read moreRead less
Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene exp ....Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene expression data supports homology between sponge and eumetazoan tissues and body plans. This project could illuminate the evolutionary history of the animal body plan.Read moreRead less
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of g ....Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of genes with fundamental roles in differentiation of the earliest cell lineages: trophoblast, pluriblast and hypoblast. The project may identify maternally localised transcripts with a marsupial-specific role in trophoblast–pluriblast specification, giving new insights into the fundamental pathways maintaining pluripotency in mammals and the evolution of the mammalian genome.Read moreRead less
Towards a new understanding of the reproductive system. The proposed analysis of the reproductive system will provide important new knowledge of gene regulation driving organ development. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.
Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to ....Non-coding RNAs in mammalian reproduction. This project aims to investigate the role of non-coding RNAs in mammalian sex chromosome biology and reproduction. Non-protein coding RNAs are a major regulatory mechanism in eukaryotic genomes; they can bind other RNAs or chromatin modifying complexes. However, the evolutionary trajectory and function of non-coding RNAs in sex chromosome biology and sexual development is largely unknown. This project will study non-coding RNAs in Australian mammals to try to answer fundamental questions about how non-coding RNAs function in mammalian sexual development.Read moreRead less
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
Sex and the dominant male determiner in Australia's true fruit flies (Diptera: Tephritidae). A novel method to separate male and female embryos of the Queensland fruit fly will enable discovery of the molecular switch that causes embryos to change from the female to the male developmental pathway when they carry a Y chromosome. The results will lead to major improvements in the control of horticultural pest insects.