Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate re ....Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate regeneration. Ultimately, this works aims to understand the metabolic requirements for regeneration. Expected outcomes include scholarly publications revealing fundamental principles of regeneration, new resources and pipelines for the research community as well as training for research students.Read moreRead less
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
Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for i ....Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for integrating nuclear actions that has the potential to create a signal transduction circuit triggered by environmental or genetic factors. This information is crucial in defining the molecular logic of signalling events that may be ultimately targeted to control cell growth, differentiation and survival.Read moreRead less
How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head ....How to build the head: A molecular mechanistic insight. This project aims to gain an insight into the functional output of the gene regulatory network and the molecular determinants that are critical for the formation of the head. Genome-wide sequencing technologies are employed to identify the ensemble of genes that are regulated by Lhx1. By a combination of bioinformatics analysis and a system biology approach, the project aims to build a model of the network of the interacting genes for head development, and to characterise the function of selected components of this network to refine its architecture and define the dynamics of the network. The knowledge may improve our understanding of the molecular mechanism underpinning the naturally-occurring variation in the forms of major body parts, and of how genes and signals work cooperatively to build an embryo.Read moreRead less
3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untra ....3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untranslated region (UTR) dynamics in eukaryotic cell biology. This project expects to significantly advance the understanding of eukaryotic gene function and gene regulation, critical in an age of personalised genomic medicine.Read moreRead less
Molecular and cellular regulation of ovarian development. This project aims to understand cell fate decisions during ovarian development. While scientists understand the decision to differentiate into a male-specific cell type, they do not understand differentiation into female-specific cell types. This team has identified marker genes that distinguish between different female cell types in the developing ovary, and will analyse the molecular and cellular mechanisms that drive the development of ....Molecular and cellular regulation of ovarian development. This project aims to understand cell fate decisions during ovarian development. While scientists understand the decision to differentiate into a male-specific cell type, they do not understand differentiation into female-specific cell types. This team has identified marker genes that distinguish between different female cell types in the developing ovary, and will analyse the molecular and cellular mechanisms that drive the development of the ovary. This could provide a deeper understanding of how genes influence cell fate decisions during embryogenesis, and the technologies developed here will be widely applicable in biotechnological research.Read moreRead less
The selective elimination of mitochondria from yeast cells: regulation and molecular mechanism . For healthy cells the quality of the mitochondrion, the cellular power plant, must be maintained. The results of this research will contribute to an understanding of the molecular mechanism for the removal of mitochondria from the cell, and ultimately inspire strategies for the treatment of diseases that result from faulty mitochondria.
The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth contr ....The Hippo signalling pathway in dividing and non-dividing cells. This project aims to understand how the Drosophila Hippo pathway performs two very different jobs in the same organ, that is control cell proliferation and differentiation. The redeployment of cellular machinery to do different jobs is very common and efficient, but the mechanism by which this occurs is poorly understood. Using new techniques, this project aims to provide new knowledge to several fields including organ growth control, cell fate specification, cellular signalling and eye vision. These discoveries are likely to enhance international collaborations and stimulate new research.Read moreRead less
Chicken and ChIPs; genetic control of avian gonadal development. This project aims to improve our understanding of gonad formation at the genetic level, using unique approaches that exploit the chicken embryo as a model system. Gonad formation during embryonic life provides an excellent model for studying the genetic control of development. The project plans to use innovative methods to study novel and known gonad-determining genes. The project seeks to make a substantial contribution to our und ....Chicken and ChIPs; genetic control of avian gonadal development. This project aims to improve our understanding of gonad formation at the genetic level, using unique approaches that exploit the chicken embryo as a model system. Gonad formation during embryonic life provides an excellent model for studying the genetic control of development. The project plans to use innovative methods to study novel and known gonad-determining genes. The project seeks to make a substantial contribution to our understanding of cell fate decisions, sex determination and gonad development. It also potentially has application to the poultry industry by illuminating those genes and pathways that can be targeted to modulate sex determination in chickens, which is a goal of the industry.Read moreRead less
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less