- Total grants
- Total funders
- Total recipients
- Earliest award date
- 17 Oct 2005
- Latest award date
- 30 Sep 2018
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
The lymph node is a meeting point for lymphocytes with antigen-presenting cells, and rapidly expands during immune responses. Lymph node structure is highly compartmentalised, and the complex internal architecture is maintained during lymph node expansion. Therefore, mechanisms must exist to balance lymph node integrity with the need to remodel very rapidly. Fibroblastic reticular cells (FRCs) are the most abundant lymphoid stromal cell population, and span the full volume of the tissue. They provide structural support and are highly contractile. FRCs ensheathes bundles of extracellular matrix, termed the conduit, which filters draining lymph. The Acton lab works to understand how lymph nodes are remodeled during expansion and has shown that interaction between FRCs and dendritic cells change FRC behaviour. This project asks how the microtubule networks within FRCs are reorganised as the FRC network expands. Phosphoproteomic screening has revealed that LL5-beta, a protein targetting microtubules to adhesion sites is regulated by interactions between FRCs and dendritic cells. This may provide a mechanism by which FRCs uncouple from underlying matrix, and target secretion of proteases or new matrix to the expanding network. This project will investigate whether LL5-beta coordinates organization of microtubules in FRCs and whether dendritic cell contact changes LL5-beta activity.
Change detection in human auditory cortex. 07 Oct 2010
The project consists of a series of brain imaging (MEG and fMRI) and psychophysics experiments based on a new paradigm designed to reveal the factors that determine listeners sensitivity to changes in an unfolding acoustic scene. Our stimuli contain unpredictable step-changes ( temporal edges ) in the pattern of fluctuation representative of a wide range of acoustic changes. By carefully manipulating stimulus statistics preceding and following the temporal edge and recording brain and behavio ural responses, we probe the cortical networks that underlie the detection of these events. Our findings to date have already provided important new insights about change processing in the human brain, previously unobserved with classical paradigms such as the mismatch negativity (MMN). Proposed experiments (1 fMRI, 6 MEG, and 2 psychophysics) are designed to broaden our understanding of the stimulus attributes and contextual factors that underlie change detection and sketch-out the processes involved: What acoustic factors does auditory cortex monitor to detect change? Which neural systems underlie change detection and what computations do they implement? How are they affected by the perceptual state of the listener (focus of attention and decision bias)? How is low-level change detection in auditory cortex used by listeners when making decisions about sound events?
The London Pain Consortium. 07 Nov 2007
Chronic pain is prevalent and its clinical treatment remains limited. The London Pain Consortium (LPC) will advance knowledge of chronic pain mechanisms through internationally competitive research and provide multidisciplinary training of clinical and biomedical scientists to promote careers in neurobiology in general and pain studies in particular. In man and animals, we will: 1) identify molecular and genetic influences on pain processes; 2) study the integrative functions of these influenc es and their translation as therapeutic targets; 3) provide research and training resources for the wider scientific community.
Management and rehabilitation of patients with socially incompatible personality disorders at Broadmoor Hospital. Secondly an audit into the outcomes of people bought into the emergency department by police who are under the influence of methamphetamine and have suicidal ideation, at St Vincents Hospital in Sydney.
Student Elective Prize for Ms Vivienne N Hannon 29 Aug 2008
A comparison of the management of a chosen disease between the Hospital of Tropical Diseases in Ho Chi Minh City, a centre of excellence for tropical medicine, and the Hospital of Tropical Disease, London including a literature review to identify unresolved management issues of the chosen tropical disease followed by a design of a theoretical clinical trial to be undertaken to clarify these unresolved issues of management.
The 1918 influenza pandemic represents the worst outbreak of infectious disease in Britain in modern times. Although the virus swept the world in three waves between March 1918 and April 1919, in Britain the majority of the estimated 228,000 fatalities occurred in the autumn of 1918. In London alone deaths at the peak of the epidemic were 55.5 per 1,000- the highest since the 1849 cholera epidemic. Yet in the capital as in other great cities and towns throughout Britain, there was none of the panic that had accompanied earlier 19th century outbreaks of infectious disease at the heart of urban populations. Instead, the British response to the 'Spanish Lady' as the pandemic strain of flu was familiarly known was remarkably sanguine. As The Times commented at the height of the pandemic: 'Never since the Black Death has such a plague swept over the face of the world, [and] never, perhaps, has a plague been more stoically accepted.' The apparent absence of marked social responses to the 1918 influenza is a phenomenon much remarked on in the literature of the pandemic, as is the apparent paradox that despite the widespread morbidity and high mortality the pandemic had little apparent impact on public institutions and left few traces in public memory. However, to date no one has explored the deeper cultural 'narratives' that informed and conditioned these responses. Was Britain really a more stoical and robust nation in 1918, or was the absence of medical and other social responses a reflection of the particular social and political conditions that prevailed in Britain during the First World War and then medical nosologies and cultural perceptions of influenza? And if the 1918 pandemic was 'overshadowed,' as one writer puts it, by the war and the peace that followed the Armistice, what explains the similarly muted response to the Russian flu pandemic of the early 1890's, a disease outbreak that coincided with a long period of peace and stability in Britain? In this project I aim to show that, contrary to previous studies, both the 1918 and the 1889-92 Russian flu pandemic were the objects of much deeper public concern and anxiety than has previously been acknowledged and that the morbidity of prominent members of British society, coupled with the high mortality, occasioned widespread 'dread' and in some cases alarm. However, in 1918 at least, government departments and public institutions actively suppressed these concerns for the sake of the war effort and the maintenance of national morale.
Blastema formation and skeletogenesis during arm regeneration of the brittle star Amphiura filiformis: cellular and molecular characterization. 17 Jan 2014
The aim of this research project is to understand the initial stages of brittle star arm regeneration in terms of stem cell involvement, cell specification and the earliest activation of the skeletogenic gene regulatory network. The brittle star is a marine organism with a unique capability for regenerating whole arms post-amputation or after injury. To determine whether the regenerative blastema, a mass of proliferative cells giving rise to the entire structure, is composed of stem cells or dedifferentiating cells, molecular tools will be employed for their characterization. Stem cell markers and lineage tracing techniques will be used to identify the nature of the cells, their origins and migratory behaviour. The regenerating arm of the brittle star is contains several skeletal structures and the second aim of this project is to understand the cohort of signalling pathways involved in the early specification of the cell lineages which will develop into this adult tissue. This will be achieved by using molecular techniques and a candidate gene approach for studying the genes that have already been well-characterised in the closely-related sea urchin, , for which a complete gene regulatory network for the embryonic development of skeletogenic cells has been published.
Neurosteroids are naturally occurring potent modulators of type A GABA receptors in the brain. Although there are many neurosteroid metabolites, these can be characterised into two distinct classes - those that potentiate GABAA receptor function and those that inhibit. Previously we deduced where potentiating neurosteroids bind on the GABAA receptor, but the inhibitory neurosteroids remain unaffected if this site is disrupted. This concurs with the belief that such inhibitory neurosteroids bind to another discrete site onthe GABAA receptor. Its discovery will allow the function of the inhibitory neurosteroids to be explored in the brain. We will select a GABA receptor thatlacks sensitivity to inhibitory neurosteroids and use this structure in combination with GABAA receptor subunits to make chimeric and eventually pointmutated receptors to identify the inhibitory neurosteroid binding site. Once the site is found, we will disrupt its function and then observe the consequences for inhibitory synaptic and tonic inhibition. Overall, this studywill use structural, electrophysiological, imaging, pharmacological and molecular approaches with GABA receptors. This study will bring much need clarity to the role and importance of inhibitory neurosteroids in the brain.
Tuning spinal motoneurons for movement. 02 Dec 2015
My overall aim is to understand how neural circuits are organised in order to control motor behaviour. Furthermore, I aim to understand dysfunction of these circuits in disease or injury in order to form the foundation for strategies to improve motor function. My research programme includes neural circuit studies in mice and in humans. Here, I will focus on one key question: how are spinal motoneurons tuned in order to produce trains of action potentials of appropriate frequencies so as to achieve the muscle contraction required for a particular motor task? This application is based on the hypothesis that motoneurons learn these firing frequencies during development, and adjust their expression of potassium channels located at sites post-synaptic to C-boutons, large cholinergic terminals forming neuromodulatory synapses on motoneuronal somata. We will address three specific aims: Aim 1: to characterise the development of SK channels, motoneuron excitability, and C-boutons Aim 2: to determine the role of Kv2.1 channels in motoneuron excitability and and C-bouton physiology Aim 3: to establish whether homeostatic mechanisms determine motoneuron.
The external world is not static but in a constant state of flux. To understand how the brain functions, we, therefore, must investigate how it extracts relevant information from dynamic, highly fluctuating sensory signals. Olfaction is an ideal modality with which to study this question. A key sense for nocturnal and crepuscular animals, such as laboratory rodents, the comparatively simple anatomy of the early olfactory system makes it highly accessible and tractable. Turbulent airflow creates a rich temporal structure in the intensity fluctuations of natural odour stimuli. Yet, how these dynamics are processed by the olfactory system and the extent to which it uses or ignores this information remains unknown. I have recently established quantitative behavioural tools, genetic and optogenetic manipulation of the early olfactory system, electrophysiological and imaging approaches in the awake behaving mouse, and the tools to measure and generate temporally fluctuating olfactory stimuli with high bandwidth. We will now combine these approaches to tackle key questions relating to the significance of natural dynamics for the coding of sensory stimuli. 1: What information is contained in the dynamics of natural olfactory stimuli?2: To what extent do neurons represent such dynamics? 3: How are stimulus dynamics used for behavioural tasks such as navigation? 4: What are the circuits and mechanisms that support, extract information from, or compensate for stimulus dynamics? My guiding hypothesis is that temporal dynamics and coherence of natural smells are decoded by the circuitry of the early olfactory system to extract information about distance, location and the nature of olfactory objects and scenes.
Neurogenesis in the mouse telencephalon. 03 May 2007
The molecular mechanisms regulating neuronal development in the telencephalon are largely unknown. The aims of the project are twofold: (1) examine the role of the transcription factor NKX2.1 in immature postmitotic neurons of the telencephalon and (2) identify genes involved in the development of neuronal populations in the embryonic subcortical telencephalon.
Development of biological motion processing in typically developing children and adolescents and in autism spectrum disorder. 03 May 2007
1. To investigate the nature of biological motion processing in healthy adults. 2. To investigate the neurocognitive development of biological motion processing in typically developing adolescents. 3. To investigate the neurocognitive development of biological motion processing in autism spectrum disorders.
While most of the body is symmetrical with respect to the midline, a few functions, including higher order behaviours and cognitive functions in the brain, have evolved to be concentrated on one (left or right) side. Although the molecular mechanisms underlying left/right asymmetry of body organs are now fairly well understood, we still know little about how lateralised brain functions arise during development. Recent research has discovered that the parapineal, an asymmetrically positioned group of neurons in the left diencephalon, is essential for development of asymmetries in the adjacent epithalamus, but little is known about the molecular mechanisms of this regulation. Also, no region equivalent to parapineal has yet been discovered in most vertebrates including birds and mammals, whereas the molecular pathways leading to epithalamic asymmetries are likely to be conserved. This project explores how epithalamic asymmetries develop in two different species - zebrafish and chicken, first by establishing the molecular mechanisms by which the parapineal regulates this process in zebrafish, then by studying
The role of c-Jun in controlling the repair-supportive phenotype of Schwann cells in injured nerves. 17 Jan 2014
Work in the Jessen and Mirsky laboratory, using a mouse in which the transcription factor c-Jun has been inactivated in Schwann cells only (c-Jun-cKO mouse), shows that the Schwann cell response to nerve injury depends on activation of the transcription factor c-Jun in Schwann cells, and that this protein specifies the phenotype of the Bunger repair cell, a cell essential for nerve regeneration. Consequently, nerve repair is severely compromised in c-JuncKO mice. This project will address the following issues: 1) Establish an in vitro model of the regeneration deficit in c-Jun-cKO mice, using adult DRG neurons and Scwann cells from injured nerves. 2) Use this model to analyse Schwann cell factors that control axon growth and neuronal survival. 3) Test whether axonalregeneration and neuronal survival can be improved by enhancing Schwann cell c-Jun expression. 4) Determine whether the diminishing ability of distal nerve tosupport repair with time after injury ( the deterioration of the distal stump ) is due to instability of the Bungner repairsupportive phenotype, and its gradual attenuation. 5) Test whether the repair-supportive Schwann cell phenotype