Molecular characterization of the role of menin in embryonic development. Menin is a protein that is necessary to prevent development of tumours. Deletion of menin in mice causes embryonic death. We think this is because menin is necessary in the placenta. This project will examine the role of menin in the fetus and the placenta, and provide information about how normal pregnancy and fetal growth is controlled.
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
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation ....Endocardial sprouting and mechano-signalling in heart trabeculation. This project aims to understand how the ventricles, the pumping chambers of the mammalian heart, form during embryonic life. Critical is the elaboration of trabeculae, myocardial projections that form a sponge-like layer on the inner surface of the chamber wall and which play vital roles in contraction, oxygen and nutrient exchange, conduction and septation. The project expects to develop a deeper understanding of trabeculation using high resolution, single cell methodologies, and to investigate how bio-mechanical forces from contraction or blood flow influence chambers formation.Read moreRead less
Genetic control of germline progenitor cell heterogeneity and fate. Tissue maintenance in adults is dependent on resident stem cells, defined by self-renewal and differentiation capabilities. It is apparent that stem cell populations are heterogeneous, being composed of subpopulations with distinct properties. The functional significance of these subsets and mechanisms that control their divergent characteristics are unclear. Using germline stem cells from mice as a model, stem cell subsets have ....Genetic control of germline progenitor cell heterogeneity and fate. Tissue maintenance in adults is dependent on resident stem cells, defined by self-renewal and differentiation capabilities. It is apparent that stem cell populations are heterogeneous, being composed of subpopulations with distinct properties. The functional significance of these subsets and mechanisms that control their divergent characteristics are unclear. Using germline stem cells from mice as a model, stem cell subsets have been identified based on differential expression of the pluripotency gene Pou5f1. This project aims to define functional characteristics of these subpopulations and to dissect transcription factor networks controlling their development. This promises important insights into understandings of adult stem cell regulation.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
Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normal ....Genetic control of tissue growth in animals. This project aims to understand how the animal body grows. This project expects to generate new knowledge and understanding of the genetic programs that govern the size and shape of animal tissues, through use of cutting-edge genome editing approaches in laboratory animals. Expected outcomes of this project include the production of genetically engineered animals with altered tissue growth, development of new theories for how tissue growth is normally controlled and how it can be manipulated industrially. This should provide significant benefits, impacting stem cell biology (improving stem cell production), tissue engineering (improving growth of artificial tissues), veterinary science and agriculture (improving productivity).Read moreRead less
Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will incl ....Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will include gain of substantial insight into molecular mechanisms underlying germline stem cell function and gene regulation within the male germline. This should provide significant benefits, including advancement of reproductive science and development of systems applicable for animal germline preservation and manipulation.Read moreRead less
cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging ....cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging in zebrafish and a new generation of biosensors to gain a vastly deeper understanding of how force controls vessel formation.Read moreRead less