Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.Read moreRead less
Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover th ....Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100130
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will b ....Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will be used to understand the biological function of the DNA sequencing results that are obtained. The equipment will allow Australian researchers to compete on an equal footing with the international leaders in understanding the roles played by genes in plants, microorganisms, animals and humans.Read moreRead less
Head and face development: dissecting tissue-specific gene function. The outcome of our investigation of the early development will inform us of the ways and means for the embryo to assemble the essential building blocks of the body, and insights into the developmental origin of birth defects. This knowledge will benefit the biomedical research community, the education sector and the general public by enabling the formulation of new hypotheses, enriching the curriculum, and providing an evidenc ....Head and face development: dissecting tissue-specific gene function. The outcome of our investigation of the early development will inform us of the ways and means for the embryo to assemble the essential building blocks of the body, and insights into the developmental origin of birth defects. This knowledge will benefit the biomedical research community, the education sector and the general public by enabling the formulation of new hypotheses, enriching the curriculum, and providing an evidence-based understanding of the genetic basis of congenital malformations for delivering informative counselling. The technical expertise gained from this project will enhance the nation's research capability through the sharing of skills and knowledge with other research teams in the academia and the industry. Read moreRead less
Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a fra ....Integration of Cellular Gene Regulation Processes. This research program aims to identify specific transcriptional regulatory networks in yeast, to determine how some of these networks interact with each other and within these networks to identify the roles of genes whose functions are currently unknown. It will identify systems regulating genes concerned with one-carbon metabolism, cellular responses to oxidative stress and developmental changes associated with meiosis. It will provide a framework to test regulatory network models and to analyse the molecular basis of interactions between control systems. This research will eventually provide the ability to predict how cells respond to drugs and other environmental stimuli.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100894
Funder
Australian Research Council
Funding Amount
$361,140.00
Summary
Nanolamps: unlocking targeted gene silencing in deep tissue with nanoparticle-based light sources. In order to better understand the function of genes, this project will develop a new method of tightly targeted gene silencing deep inside of the body by nanoscale light sources. This will shed new light on the nervous system and, in the first instance, help to elucidate the role of the PACAP neurons in blood pressure regulation.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560987
Funder
Australian Research Council
Funding Amount
$156,697.00
Summary
Robust High Resolution Gene and Protein Expression Analysis Facilities in WA. Biological research is playing an increasingly important role in keeping agriculture internationally competitive and helping to unravel the basic mechanisms underpinning plant and animal health. This collaborative research equipment will greatly enhance and extend our existing functional genomic facilities in WA, allowing robust pre-fractionation of samples for directed proteomic analysis within complex systems and al ....Robust High Resolution Gene and Protein Expression Analysis Facilities in WA. Biological research is playing an increasingly important role in keeping agriculture internationally competitive and helping to unravel the basic mechanisms underpinning plant and animal health. This collaborative research equipment will greatly enhance and extend our existing functional genomic facilities in WA, allowing robust pre-fractionation of samples for directed proteomic analysis within complex systems and allowing accurate and sensitive measurement of gene expression. Both of these are critical for analysis of low abundance components involved in signalling and regulatory functions in biological samples.Read moreRead less