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
Magnetically controlled drug release from tissue scaffolds for the treatment of acute burns. Severe skin burns are frequently associated with functionally disabling scarring and the risk of death. New magnetically activated wound seals for the treatment of acute burns will be developed that reduce the need for frequent painful dressing changes and hence facilitate rapid healing with a significantly reduced chance of scarring.
Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem ....Touch and Tension: Molecular Determinants of Human Mechanosensation . Feelings of touch and muscle tension are initiated by mechanosensory neurons found within the peripheral nervous system. Knowledge of human mechanosensory neurons has predominantly relied on rodent studies because of the limited availability of human tissue, which is not ideal. Our team has developed novel technologies for generating human mechanosensory neurons ‘in the dish’. The major aim of this project is to use human stem cell-derived mechanosensory neurons as a platform to extensively study their molecular and functional properties. The significant benefits are the advancement of knowledge in the human mechanosensory system, which to date has been lacking, and in the long-term progress commercial development of novel drugs.Read moreRead less
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
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.
Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcripti ....Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcription on a genome-wide scale and will thereby reveal the full extent of mechanisms by which these important genetic switches control gene expression networks the characteristics of cells. This is of fundamental significance to our understanding of gene regulation.Read moreRead less
Synthetic regulators of gene expression. RNA plays many essential roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis. Despite these realisations the current approaches to manipulate RNA are limited in many respects. This project will use synthetic biology approaches to engineer synthetic regulators of RNAs in living cells. These studies will provide new tools for use in biological research and provide insights into h ....Synthetic regulators of gene expression. RNA plays many essential roles in cells, from information transfer and regulation of gene expression to scaffolding macromolecular structures and catalysis. Despite these realisations the current approaches to manipulate RNA are limited in many respects. This project will use synthetic biology approaches to engineer synthetic regulators of RNAs in living cells. These studies will provide new tools for use in biological research and provide insights into how natural proteins control gene expression. Furthermore, this project will use these tools to understand the mechanisms of how proteins are synthesised in mammalian mitochondria.Read moreRead less
Understanding protein-nucleic-acid interaction networks in cold-adapted archaea. The aim of this project is to learn how microorganisms can function effectively in naturally cold environments. Results will determine how important cellular processes occur when microorganisms grow in the cold, and hence why they are able to maintain a natural balance in ecosystems such as Antarctica.
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less