The Stemformatics gene expression compendium: development of multivariate statistical approaches for cross platform analyses. Scientific data is gathered in many different forms, but there are significant gaps in our ability to analyse multiple datasets when generated on different pieces of equipment. This project will study three typical research questions in stem cell biology to develop new analytical approaches to help solve this major data gap.
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
Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of ....Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of way in which respiratory gene expression is controlled in bacterial species for which Escherichia coli is not a suitable model. Read moreRead less
Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPI ....Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPIs)”. This project plans to couple advanced physiological and functional genomics techniques to transform our understanding of how algal symbiont metabolic KPIs regulate coral growth and stress susceptibility. This may provide new diagnostic capability for the assessment of coral health and may enable us to improve coral reef ecosystem management.Read moreRead less
Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that t .... Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that the true nature of brain adaptation across the lifespan will be revealed. Findings which may then provide new opportunities to strengthen, maintain and optimise cognitive function.Read moreRead less
Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the ....Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.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.
Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenet ....Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and memory formation, the findings of the project will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less