Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods ....Benchmarking the neurophysiology of human cortex models in vitro. This project aims to improve human brain models in vitro by developing an analytical tool benchmarking biophysical similarities to the adult human cortex. This project expects to generate new knowledge by testing for the first time the theory that integrating sensory-like inputs and awake/sleep-like cycles of electrical activity in vitro may complete the maturation of human brain organoid models. It will also generate new methods to simplify the analysis of multimodal path-clamping data (Patch-seq). Expected outcomes will facilitate research collaboration and the reproducibility of accurate experimental replicates of the human brain. This will provide significant benefits in the global race to understand human brain computation mechanisms.Read moreRead less
Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting ....Functional analysis of long noncoding RNAs expressed in the brain. For many years, the mammalian genome has been thought to be mainly junk. Recently, however, it has become evident that most of the genome specifies RNAs that do not encode proteins ('long noncoding' RNAs, lncRNAs), many of which are brain-specific. This project aims to determine the functions of lncRNAs that are expressed in the hippocampus (involved in learning) and the cerebellum (involved in movement coordination) by deleting them in mice, testing for developmental, cognitive and motor effects, and characterising the structures with which they are associated. The results of the project are expected to open new vistas in neuroscience, contributing to understanding the molecular basis of brain function and the 'dark matter' of the genome.Read moreRead less
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understandin ....Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understanding of olfaction in insects, increased national and international collaboration, and outstanding graduate student training. This research will be of significant future benefit in deriving methods to modify the behaviour of insects of agricultural or medical importance, for example the sheep blowfly. 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
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.Read moreRead less
Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model t ....Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model to generate new knowledge of the cellular and genetic components that drive evolution of different brain parts and shapes the vertebrate brain. In doing so the project aims to provide research training, excellence and knowledge that in future may benefit health and the society. Read moreRead less
The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.Read moreRead less