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.
Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, ....Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, hold enormous economic potential for applications ranging from biomedicine to biofuel production. This project aims to help synthetic biologists to embed made-to-order circuits in appropriate host cells to act as living factories, potentially replacing industrial processes which are currently environmentally and economically costly.Read moreRead less
Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipu ....Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipulate HIF for pharmaceutical benefit.Read moreRead less
Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how t ....Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how the atypical cadherin FAT4 relays mechanical signals including flow and tension to the lymphatic endothelial cell skeleton, thereby enabling changes in cell shape important for building lymphatic vessels. This project will increase our understanding of how cells sense touch and may be applied for tissue engineering purposes.
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Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
The rational design and construction of new genetic circuits for applications in synthetic biology. By designing, building and testing new gene control modules, this project will gain an understanding of the design principles required for the construction of biological circuits with predictable and controllable behaviour. The ability to build such circuits will have significant economic benefit in areas such as metabolic engineering and biomedicine.
Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be use ....Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be used to construct and control purpose-built genetic networks and pathways. The results of this project are expected to add to the molecular tookit available to synthetic biologists.Read moreRead less
Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less
Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregul ....Innovative Approaches for Defining the Interaction of Insulin like Growth Factor I (IGF I) with the Type 1 IGF Receptor. This study will improve our understanding of the interactions of Insulin-like Growth Factors (IGFs) with their principal receptor, the IGF-1R. A sound understanding of these interactions is essential for the development of non-peptide IGF antagonists designed for therapeutic applications. Such molecules could lead to new therapeutic approaches for diseases in which dysregulation of the IGF system has been implicated including cancer, diabetes and atherosclerosis.
Since IGFs are major determinants of growth, the outcomes of this project could also lead to improvements in animal production with major benefit to primary industry. New IGF analogues developed could assist biotechnology exports.
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Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the id ....Cell death by self-eating: Autophagy-dependent tissue removal. This project aims to study the mechanisms and regulation of autophagy-dependent cell death. Cell death maintains cell and tissue homeostasis. Although most cell death is mediated by apoptosis, other modes of cell deletion have emerged recently. One form of cell death involves autophagy, the catabolic process of cellular self-digestion through lysosomal enzymes. As autophagy is a default mechanism of cell survival under stress, the idea of autophagy-dependent cell death has been controversial. This proposal aims to resolve this question and provide highly topical knowledge of broad biological significance.Read moreRead less