Understanding the potency and role of individual stem cells in the skin using Rainbow technology. To renew itself, the skin and its components rely on the activity of stem cells. This project will define more precisely the role of each individual stem cell by labelling them with a unique colour and following its fate. This project has the potential to change our current view on how the skin maintains and repairs itself.
Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve ....Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve cells, by tracking the impact of the activity of signalling pathways and gene regulation on cell differentiation. This may deliver insights into the temporal hierarchy and functional attributes of the molecular switches that control stem cell differentiation. Expected outcomes may have applications in tissue engineering.Read moreRead less
A molecular paradigm of organ formation during embryonic development: the role of RhoGTPase. How do cells in the embryo acquire the correct shape and structure to form tissues and organs? This project will reveal the genes and proteins required for the formation of the early gut and associated organs and will enhance our understanding of how organs are constructed from the building blocks in the embryo.
Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and w ....Enhancing neurogenesis in the adult primate brain. New neurons are robustly generated in the subependymal zone (SEZ) during human development. Thus, the SEZ may represent an endogenous modifiable source of neurons to enhance plasticity and therapeutic potential in the brain. However, despite our preliminary data, SEZ neurogenesis beyond the first months of life is controversial. This project aims to understand changes in the capacity for human SEZ proliferation from birth through to ageing and whether neurogenesis may be induced by inflammation in the adult. Using transcriptomics we will also determine how the neurogenic environment changes with age/inflammation. This project is an important step in proving that the brain's potential to generate new neurons extends beyond infancy.Read moreRead less
Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study wi ....Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study will significantly advance our understanding of gene regulation and mechanisms for controlling protein levels and contribute to a deeper understanding of brain function during development and aging.Read moreRead less
The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a funct ....The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a functional, signalling role. The research will determine how these fibrils form and how the structures confers biological function. It could identify features in these fibrils that can be targeted as a means of ultimately preventing tissue damage after heart attack and stroke.Read moreRead less
Inhibiting protein-protein interactions involved in neural development and disease. This project will determine the molecular mechanisms by which the protein LMO4 (a regulator of brain development) binds to DEAF1 (which also regulates neural development) and CtIP (which protects against tumour formation). This will allow a set of reagents to be developed to help determine the functions of LMO4, and may ultimately be used to treat disease.
Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their ge ....Links between DNA replication and chromosome end maintenance. This project aims to increase knowledge of the way in which cells maintain their genomes, including the ends of their chromosomes, to enable their own survival. The ends of chromosomes (telomeres) are essential for survival and proliferation of the cells of most organisms. This project aims to determine the molecular details of a recently discovered link between telomere maintenance and the way cells maintain the integrity of their genome. This is likely to lead to increased understanding of the fundamental biological process of genome maintenance, representing a significant scientific advance. The project expects to have far-reaching implications for biotechnology applications that require the survival of cells.Read moreRead less
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.Read moreRead less
Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for gener ....Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for generating cellular diversity and enable identifying unique precursors and the evaluation of the efficacy of deriving the biological relevant cell types from the stem cells. This project expects to have a significant impact on the translation to cell production methodology for tissue engineering and bioreactor technology.Read moreRead less