Below is a brief outline of the projects available, more detailed information can be found on the University website or by emailing the lead supervisor
Neuropsychological evaluating of the cortical underpinnings of pathological pain (43)
Many chronic pain conditions cannot be completely explained by any pathology in the painful site. Using neuropsychological testing of people with chronic pain and normal controls, this project will investigate the possibility that such conditions may arise due to changes in motor control and sensory processing in the brain.
Key Words: Translational research; pain; body representation; neuropsychology; perception and action
The neural network basis of essential tremor (46)
Essential tremor is the most common type of neurological disorder, involving abnormal rhythmic activity in large scale brain networks. This project will use the combined power of basic, theoretical and clinical neuroscience approaches to investigate the neural network basis of tremor.
Key Words: Tremor, motor systems, brain networks
Is the ubiquitin ligase Siah1 neuroprotective in Alzheimer’s disease? (50)
Early features of Alzheimer’s isease include mitochondrial and synaptic dysfunction. This PhD will test the hypothesis that manipulating the interactions between mGluRs, the ubiquitination and SUMOylation pathways, and the mitochondrial GTPase Drp1 can protect neurons and may help delay or prevent the onset of dementia.
Key Words: Alzheimer’s disease, synaptic plasticity, mGluRs, SUMOylation, ubiquitination
Modelling the consequence of epigenetic variation in Alzheimer’s disease (51)
We have identified a number of epigenetic events associated with Alzheimer Disease (AD), using mutations in Drosophila homologues of these genes you will measure resulting changes in age-dependent neurodegeneration, electrophysiology, memory, sleep and lifespan in order to go onto screen for new treatments or genetic interactors to improve AD-related pathology.
Key Words: Alzheimer disease, epigenetics, neurodegeneration, memory, Drosophila
Stress and Epilepsy: The role of glucocorticoids in modulating seizure occurrence (54)
An exciting opportunity to become part of two world-leading research centres focussed on in vivo physiology (Bristol) and mathematical modelling (Exeter). This project will focus on unveiling the mechanisms by which stress responsive hormones can modulate brain network dynamics and increase the likelihood of seizures in susceptible individuals.
Key Words: Neuroendocrinology, stress, epilepsy, dynamics, glucocorticoid
Epilepsy on a diamond dish: Genetically engineered neuronal networks for the targeted study of Epilepsy on diamond multiarray electrodes (55)
Understanding the physiology of neurons with altered excitability is crucial for the treatment of epilepsy. Using a cross-disciplinary approach encompassing diamond multi-electrode arrays, induced pluripotent stem cell technology and CRISPR-Cas9 engineering we will study epileptogenic human neuronal networks in vitro. Aiming to uncover targetable network phenotypes for high-throughput drug screening.
Key Words: iPSCs, artificial neuronal networks, biomaterials, epilepsy, diamond
Newborn Brain Injury: The role of Glutamate Transport regulation (56)
Newborn brain injury is a major cause of long-term neurodisability globally. This translational project will investigate the role of epigenetics in glutamate transporter function and the potential of glutamate transport manipulation in protecting the developing brain.
Key Words: Neurodisability, Hypoxic Ischaemic Brain Injury, Newborn, Epigenitcs, Glutamate Homeostasis
Cellular decoding of gonadotropin-releasing hormone (GnRH) dynamics (57)
The reproductive system is controlled by GnRH secreted from hypothalamic neurons. This secretion is pulsatile and GnRH effects are dependent on pulse frequency. We will explore how cells decode GnRH dynamics in an interdisciplinary project combining wet-lab studies (automated fluorescence microscopy for signal pathway reporters) with deterministic and stochastic modelling.
Key Words: Neuroendocrinology, cell signalling, mathematical modelling, stochastic modelling, reproductive endocrinology
Relating noradrenergic neuronal structure to function in human health and disease : defining novel biomarkers with magnetic resonance imaging (61)
Dysfunctions of noradrenergic brainstem neurons have recently been implicated in the early pathogenesis of several neurological diseases (e.g. Alzheimer’s) and chronic pain conditions. This project will develop and validate novel magnetic resonance imaging techniques (e.g. tractography) to investigate anatomical and functional connectivity of noradrenergic neurons in the human brain.
Key Words: noradrenaline, connectivity, functional MRI, tractography, neuro-degeneration
Investigating the therapeutic potential of newly identified gene targets using stem cell models of human neurodegenerative disease (63)
Many human neurodegenerative diseases are characterised by impaired protein and mitochondrial metabolism. A screen of 7500 genes identified thirty that modulated mitochondrial function; in this project human stem cell disease models coupled with molecular, imaging and genomic techniques will be used to characterise gene function and therapeutic potential.
Key Words: Neurodegenerative-disease, stem cells, mitochondria, therapy
Pathways to psychosis: examining whether potentially modifiable cognitive processes mediate the effect of childhood trauma on psychosis (66)
The aim of this project is to understand the relationship between childhood traumatic experiences and adult psychotic outcomes. Furthermore, the project aims to identify potentially modifiable cognitive processes that might mediate this relationship and explain how biological/psychological effects of traumatic stress lead people to hear voices or develop paranoid beliefs.
Key Words: Psychosis; traumatic stress; epidemiology; cognitive neuroscience; statistical modelling
Gut-brain axis dysfunction in mouse models for autism spectrum disorders (67)
This PhD project is focused on the interaction between gut and brain functions in Autism Spectrum Disorders (ASD). The PhD applicant will use genetic mouse models for ASD to analyse the role of genetic risk factors for ASD in digestion and determine causal links between gut dysfunctions and ASD symptoms.
Key Words: Mouse models, autism, microbiome, gut-brain axis, behaviour
Sites of active gene regulation in the developing human brain and their role in neuropsychiatric disorders (68)
This project will use cutting-edge laboratory and bioinformatic techniques to identify regions of the genome that regulate gene expression in the developing human brain. These data will be integrated with other genomic datasets including those from studies of neuropsychiatric disorders to help elucidate genetic risk mechanisms for these conditions.
Key Words: Brain development, (epi-)genomics, gene regulation, ATAC-Seq, neuropsychiatric disorders.
Synaptic and circuit development in cerebral cortex in a mouse model of schizophrenia (72)
This project will examine the effect on cortical development of disrupting the function of the “disrupted in schizphrenia” (DISC1) gene using chronic and acute 2-photon imaging to measure synaptic properties and neuronal circuit assembly.
Key Words: Development, synapse, neuroscience, schizophrenia, plasticity
Neurocellular, functional genomic and bioinformatics analysis of the mechanism of CHD2 in childhood onset epileptic encephalopathy. (73)
This inter-disciplinary project investigates the function and targets of the chromatin re-modeller CHD2, a genetic cause of childhood epilepsy, and combines stem cell and neurobiology with genomic and bioinformatics analysis. Training is provided in stem cell biology, neuroscience and bioinformatics and would suit individuals with any of these backgrounds.
Key Words: Epilepsy, epigenetics, human stem cell biology, functional genomics, bioinformatics
Overnight therapy: treating PTSD through sleep engineering (76)
Recollection of persistent traumatic memories in PTSD is linked to suicide and depression. We aim to develop a non-invasive treatment for PTSD through manipulation of sleep. Negative memories can become less upsetting if they are neurally reactivated during sleep. We will explore neural reactivation at systems and cellular levels.
Key Words: Sleep, PTSD, memory, neural networks
Functional dissociations within the medial temporal lobe memory system: In vivo high field imaging in humans and rats (79)
This project will utilize advanced neuroimaging and behavioural techniques for the in vivo investigation of functional dissociations within the medial temporal lobe memory system. Translational studies in humans (healthy adults, Mild Cognitive Impairment) and rats will provide new insights into the neural correlates underlying age- and disease-related memory impairments.
Key Words: Fornix, hippocampus, memory, Mild Cognitive Impairment, Magnetic Resonance Imaging
The impact of genetic and intra-uterine risk exposures on early child neurodevelopmental impairments (82)
Genes and environmental factors both contribute to neuropsychiatric disorders. Many of these disorders are preceded by neurodevelopmental impairments in early childhood. This PhD involves examining the impacts of composite measures of psychiatric genetic risk, intra-uterine risk and protective exposures and their interplay on early neurodevelopmental impairments.
Key Words: Child mental health, neurodevelopment, population, genetics, epidemiology, prenatal
Chemical probes of O-GlcNAc modification and amyloid plaques for diagnosis of Alzheimer’s disease (84)
The project aims to develop novel diagnostic techniques for Alzheimer’s disease through chemical probes of O-GlcNAc modification and amyloid plaques. This highly collaborative and interdisciplinary project combines our expertise in synthetic chemistry, biomedical imaging and neurophysiology from three research groups in Cardiff and Exeter.
Key Words: Alzheimer’s disease, diagnostic, O-GlcNAc modification, amyloid, imaging
High resolution functional imaging of the human brainstem using 7 Tesla MRI: understanding blood pressure control and hypertension (86)
We will map the circuits in the human brain that are involved in the control of blood pressure. By combining physics and physiology expertise, we will use advanced functional MRI at ultra-high field strength (7T) to visualise the relevant brainstem centres, helping us to understand better the causes of high blood pressure.
Key Words: Functional magnetic resonance imaging (fMRI), hypertension, brainstem
Relationship between synaptic dysfunction and degeneration in a rodent model of dementia (87)
Synaptic dysfunction plays a key role in the cognitive decline seen in dementias such as Alzheimer’s disease. This PhD project will examine the function of individual synapses in a mouse model of dementia, using whole-cell electrophysiology and in vivo two-photon imaging techniques.
Key Words: Alzheimer’s disease; dementia; synapses, two-photon imaging; electrophysiology
Defining the contribution of hypothalamic astroglia to the homeostatic regulation of food intake (89)
Dysregulation of food intake contributes to obesity, a major health issue in the U.K. The brain regulates food intake by integrating nutritional, nervous and hormonal cues. Utilizing an integrative physiological approach this project will focus on understanding of the contribution of glia to the neural circuits that regulate food intake.
Key Words: Obesity, Astrocyte, Electrophysiology, Feeding, Neuroendocrinology
Identifying Novel Blood Biomarkers of Alzheimer’s disease (91)
The identification of novel biological markers (biomarkers) for Alzheimer’s disease (AD) will allow earlier and more successful treatment. This project will integrate genome-wide genetic, epigenetic and gene expression measures in blood from AD patients with detailed clinical, epidemiological and neuroimaging data with the aim to identify unique biomarkers for AD.
Key Words: Alzheimer disease, epigenetics, biomarkers, DNA methylation, bioinformatics
Developing and Testing Methods of Precision Medicine in Clinical Trials for the Psychological Treatment of Depression (97)
This studentship will develop new ‘precision medicine’ statistical techniques and models to help clinicians accurately prescribe different psychological treatments for depression. These models will predict clinical outcomes based on measureable patient and therapy characteristics. This translational project will develop the students statistical, health services research and clinical trials expertise.
Key Words: Depression, Psychological-Therapy, Precision-Medicine, Prognosis, Clinical-Trials