Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less
RNA-based analysis for prediction of islet death in diabetes. Death of insulin-producing cells is a common feature in diabetes. Presently, a blood glucose test remains the only blunt instrument to diagnose diabetes. The RNA-based analysis for prediction of islet death in diabetes (RAPID) study links with eight clinical trials to test this newly developed non-invasive assay for predicting diabetes. Early diagnosis will help to reduce diabetic complications in later life.
Discovery Early Career Researcher Award - Grant ID: DE190100116
Funder
Australian Research Council
Funding Amount
$415,737.00
Summary
Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically recons ....Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically reconstruct gene regulatory networks. These networks are the molecular basis for understanding human cells. This projects outcomes intend to include the first reference single-cell regulatory database and novel methods and software to predict individual cells. This project will contribute to advancing Australia's capabilities in single-cell, precision medicine, and big biological data analysis leading to significant scientific, societal and commercial benefits.Read moreRead less
Investigating spermatogonial stem cell allocation in the fetal testis. This project aims to determine when and how spermatogonial stem cells (SSCs) are specified, and whether a genetic pathway that is used by in vitro stem cells is also employed, in vivo, by testicular stem cells. The project aims to deliver insight into the mechanisms of adult stem cell specification and regulation, in general. Intended practical outcomes of this work will underpin new methods for fertility management in animal ....Investigating spermatogonial stem cell allocation in the fetal testis. This project aims to determine when and how spermatogonial stem cells (SSCs) are specified, and whether a genetic pathway that is used by in vitro stem cells is also employed, in vivo, by testicular stem cells. The project aims to deliver insight into the mechanisms of adult stem cell specification and regulation, in general. Intended practical outcomes of this work will underpin new methods for fertility management in animals (in agriculture and conservation of endangered species) and humans. Knowledge gained will inform our understanding of stem cell biology more broadly and guide efforts to treat infertility or control fertility in animals and humans.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100652
Funder
Australian Research Council
Funding Amount
$345,000.00
Summary
Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is h ....Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is how the balance between self-renewal and differentiation is regulated in these cells, nor how the control of this fate decision impacts on optimal organ development. This project aims to dissect the molecular identity, regulation, and influence of this stem cell population on kidney development.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100976
Funder
Australian Research Council
Funding Amount
$307,058.00
Summary
Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-o ....Identifying parent-of-origin effects and their impact on complex traits. This project aims to systematically identify genetic variants whose effects depend on whether they were inherited from the mother or the father, and to assess their impact on complex human traits. Most gene mapping studies to date assume that the effects of genetic variants are equal regardless of the parent of origin, thus have not explored this source of genetic variation. However, animal studies indicate that parent-of-origin specific effects (POEs) are important contributors to variability of developmental and behavioural traits. Leveraging genetic and epigenetic data from some of the world’s largest cohorts, this project will improve our understanding of POEs on complex human traits related to early development, growth and behaviour.Read moreRead less
Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technolo ....Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technologies and transgenic mice to identify the suite of Sox9 target genes and partner proteins. Anticipated outcomes include insights into sex determination, stem cell differentiation, and development of many other organ systems that depend on Sox9 function, providing proof-of-concept for high-throughput analysis of molecular control networks in the embryo.Read moreRead less
Modelling stem cell decisions in mouse germ cells. A fundamental problem in biology is how cells transition from pluripotency to lineage commitment. The aim of this project is to study this problem, in vivo, by dissecting the mechanisms active during normal development of primordial germ cells (PGCs, gamete stem cells) in the mouse fetal testis. Using molecular, cellular and whole animal assays three central hypotheses will be addressed regarding genes likely to be important in the process. This ....Modelling stem cell decisions in mouse germ cells. A fundamental problem in biology is how cells transition from pluripotency to lineage commitment. The aim of this project is to study this problem, in vivo, by dissecting the mechanisms active during normal development of primordial germ cells (PGCs, gamete stem cells) in the mouse fetal testis. Using molecular, cellular and whole animal assays three central hypotheses will be addressed regarding genes likely to be important in the process. This research will reveal the molecular nature of bipotential switches in cell identity and will inform some of the most important biological issues of our time, including tissue regeneration, aging and cancer biology.Read moreRead less
Molecular regulation of the mitosis-to-meiosis switch in germ cells. This project will build on our recent major discoveries to study how sperm and oocyte production begins during fetal life. This issue is critical for understanding fertility and infertility in animal species and humans. The answers generated will lay the groundwork for fertility control in humans, pets, pests and endangered animals.