Defining The Role Of Genetic Variants In Systemic Lupus Erythematosus: Copy Number Variants And Epigenetic Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$338,625.00
Summary
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease associated with increased risk of mortality, severely impacting the quality of life for those affected. A large number of genes have been implicated in SLE susceptibility, however we know little of the genetic mechanisms proceeding disease onset. This project uses state of the art technology to define the role of genetic variants in SLE susceptibility and identify their importance across patients of different ethnic backgrounds.
Genetic factors responsible for risk of breast and prostate cancer are largely unknown. Mutations in genes currently known to be associated with susceptibility only account for a small proportion of the familial aggregation of these cancers. I will be applying new genetic technology to population-based studies of cancer to identify new genetic and epigenetic markers of cancer risk. I will use this information to improve health care for families with prostate and breast cancer.
As a molecular geneticist, I am interested in how and why genetic mutations occur, how these changes cause disease or disease predisposition, and ways of better treating and monitoring genetic disease. The ‘model diseases’ I am most interested in are blood cell diseases such as autoimmunity (e.g. arthritis) and leukaemias.
Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRN ....Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRNAs expression in the packaging and maintenance of retrotransposons. Understanding this fundamental question will advance the scientific knowledge of small RNA functions in our genomic defense systems. Read moreRead less
Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
Silencing the X chromosome: why and how. The project aims to understand why we have X chromosome inactivation, and examine the fundamental molecular mechanisms of how it is achieved. The project will explore RNA-mediated epigenetic modification of whole chromosomes with innovative molecular methods in placental mammals, and also iconic Australian mammals, to transform our understanding of X chromosome inactivation. Further understanding whole chromosome silencing, will inform future research int ....Silencing the X chromosome: why and how. The project aims to understand why we have X chromosome inactivation, and examine the fundamental molecular mechanisms of how it is achieved. The project will explore RNA-mediated epigenetic modification of whole chromosomes with innovative molecular methods in placental mammals, and also iconic Australian mammals, to transform our understanding of X chromosome inactivation. Further understanding whole chromosome silencing, will inform future research into potential therapies for chromosomal trisomies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100460
Funder
Australian Research Council
Funding Amount
$380,000.00
Summary
Role of DNA methylation in response to low nutrient availability in plants. DNA methylation (mC) is a covalent modification of DNA essential for the establishment and maintenance of correct gene expression patterns and recently suggested to be responsive to some environmental cues in plants. Using cutting edge technologies, this project aims to identify nutrient stress-induced mC changes and investigate the role that these changes may play in transcriptional regulation, as well as assessing whet ....Role of DNA methylation in response to low nutrient availability in plants. DNA methylation (mC) is a covalent modification of DNA essential for the establishment and maintenance of correct gene expression patterns and recently suggested to be responsive to some environmental cues in plants. Using cutting edge technologies, this project aims to identify nutrient stress-induced mC changes and investigate the role that these changes may play in transcriptional regulation, as well as assessing whether these changes can be transmitted to the next generation to confer intergenerational stress responsiveness. Altogether this project aims to provide fundamental knowledge of the role of mC in plant gene regulation and stress response as well as paving the way for the next generation of novel crop-improvement strategies.Read moreRead less
HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility. This project is to define the biochemistry of a previously uncharacterized protein in male fertility using a unique mouse model and innovative DNA and protein technologies. This project will define a novel, and essential, pathway for male fertility and may ultimately have relevance to the maintenance of health or improving fertility.
Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation ar ....Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation array data from thousands of blood samples from human subjects will be statistically analysed to develop and validate predictors for chronological age, smoking, caffeine use, pesticide exposure, diet and body mass index. Potential applications of epigenomic prediction are widespread, ranging from forensics to ecology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101450
Funder
Australian Research Council
Funding Amount
$374,300.00
Summary
The molecular basis of division of labour in the beehive. This study will dissect the genes and gene networks underpinning behaviour using cutting edge molecular and computational techniques. As a model, this project will study the division of labour in a social insect, the honeybee.