What shapes our brain? This project aims to improve our fundamental understanding of the biological mechanisms that drive folding of the cerebral cortex, which occurs during development of the brain. Cortical folding is unique to humans and higher mammals, and is thought to underpin the emergence of intelligence and contribute to higher-order brain functions. This project will enhance knowledge of how the cerebral cortex folds and develop novel tools for analysing brain development. The project ....What shapes our brain? This project aims to improve our fundamental understanding of the biological mechanisms that drive folding of the cerebral cortex, which occurs during development of the brain. Cortical folding is unique to humans and higher mammals, and is thought to underpin the emergence of intelligence and contribute to higher-order brain functions. This project will enhance knowledge of how the cerebral cortex folds and develop novel tools for analysing brain development. The project will provide significant benefits including the generation of fundamental knowledge with implications for future understanding of cortical folding abnormalities in babies born preterm, following fetal growth retardation in utero, or when exposed to maternal alcohol. In the longer term, the project will contribute to improvements to human neurodevelopment and brain health.Read moreRead less
Spatiotemporal signatures of learning in brain reward systems. Learning to strengthen behaviours that secure resources and warrant survival is one of the primary functions of the brain. This Project seeks to establish the rules that govern the integration of learning in brain reward systems by studying how neuronal circuits change their molecular signatures as animals assimilate new knowledge. These studies will combine novel experimental designs to investigate learning with multidisciplinary me ....Spatiotemporal signatures of learning in brain reward systems. Learning to strengthen behaviours that secure resources and warrant survival is one of the primary functions of the brain. This Project seeks to establish the rules that govern the integration of learning in brain reward systems by studying how neuronal circuits change their molecular signatures as animals assimilate new knowledge. These studies will combine novel experimental designs to investigate learning with multidisciplinary methods for mapping, recording and functionalising teaching signals in behaving mice. The outcomes will create a significant shift in our understanding of the neural bases that underlie reward learning, and will critically expand the field by providing a new model of learning integration in brain systems.Read moreRead less
The neural basis of memory. Although they define us, our knowledge about how, and where, memories are processed and stored within the brain is still in its infancy. This project aims to investigate the morphological and functional changes that occur in cortical neurons during memory formation. By recording from both mouse and human neurons, this study will bridge the gap in knowledge between the heavily-investigated rodent brain and the human brain and advance our knowledge on how remote memorie ....The neural basis of memory. Although they define us, our knowledge about how, and where, memories are processed and stored within the brain is still in its infancy. This project aims to investigate the morphological and functional changes that occur in cortical neurons during memory formation. By recording from both mouse and human neurons, this study will bridge the gap in knowledge between the heavily-investigated rodent brain and the human brain and advance our knowledge on how remote memories are formed in individual neurons within the frontal cortex of the brain. These findings will highlight potential neural mechanisms that might be awry in cases of memory loss and amnesia.Read moreRead less
Platform technology to decode motor control through ultra high-field MRI. This project aims to advance our understanding of the poorly understood neural circuits that enable fine motor control in humans. To obtain this knowledge, new platform technology will be developed to capture the full kinematics of the hand during concurrent functional magnetic resonance imaging at ultra high-field. This device will allow testing of fundamental theories describing the canonical microcircuits involved in ha ....Platform technology to decode motor control through ultra high-field MRI. This project aims to advance our understanding of the poorly understood neural circuits that enable fine motor control in humans. To obtain this knowledge, new platform technology will be developed to capture the full kinematics of the hand during concurrent functional magnetic resonance imaging at ultra high-field. This device will allow testing of fundamental theories describing the canonical microcircuits involved in hand motion. Expected outcomes include new evidence of mirror neurons and observation of predictive error signals in the motor cortex. This new knowledge paves the way towards improved computer-brain interface technology which is likely to create benefits through translation to applications such as artificial limb control.Read moreRead less
Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform o ....Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform of immediate use in the agriculture sector and for animal model alternatives. The benefit will be widespread, ensuring the growth and sustainability of our health and agriculture sector. The project will increase public understanding of protein delivery technologies, aiding in technology adoption.Read moreRead less
Uncovering a novel memory process mediating stimulus-based decisions. The project aims to describe how environmental stimuli influence choice between actions. The goal is to demonstrate that this influence recruits a novel form of memory characterised by a durable change in the expression of an opioid receptor. It will combine sophisticated behavioural tasks with modern genetic tools in rodents to identify the molecular, cellular and neural interactions underlying the acquisition, maintenance an ....Uncovering a novel memory process mediating stimulus-based decisions. The project aims to describe how environmental stimuli influence choice between actions. The goal is to demonstrate that this influence recruits a novel form of memory characterised by a durable change in the expression of an opioid receptor. It will combine sophisticated behavioural tasks with modern genetic tools in rodents to identify the molecular, cellular and neural interactions underlying the acquisition, maintenance and retrieval of this memory. The project expects to provide new insights into the brain machinery promoting motivated behaviours and adaptive decision-making, and to extend knowledge about the physiological underpinnings of our memories. Read moreRead less
Gut-brain control of cue-induced feeding behaviours. This proposal aims to determine how food cues (e.g., advertisements) trigger our desire to eat. Using modern virally-mediated strategies, behavioural and histological techniques in a transgenic rat, this proposal seeks to characterise novel gut-brain circuits that mediate cue-induced feeding behaviours. This is significant as food cues can cause overeating, which is problematic in the current obesogenic society, yet the mechanisms are unclear. ....Gut-brain control of cue-induced feeding behaviours. This proposal aims to determine how food cues (e.g., advertisements) trigger our desire to eat. Using modern virally-mediated strategies, behavioural and histological techniques in a transgenic rat, this proposal seeks to characterise novel gut-brain circuits that mediate cue-induced feeding behaviours. This is significant as food cues can cause overeating, which is problematic in the current obesogenic society, yet the mechanisms are unclear. This project expects to provide new knowledge on how the gut communicates with multiple brain regions to control cue-induced eating. This work should benefit the advancement of knowledge and establish a framework for future research on gut-brain mechanisms in cue-induced feeding.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
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
Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate recep ....Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate receptors is regulated in neurons during plasticity and learning. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of the cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition.Read moreRead less