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Your search ‘’ returned 16 results in ‘All grant fields’

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Earliest award date
31 Jan 2017
Latest award date
27 Apr 2017
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Studying murine behaviour and extending the hippocampal place cell model to 3 dimensions
<p>In previous decades, studies focussing on hippocampal place cell activity have resorted to using 2-dimensional simulation models. I argue that such a paradigm proves to be insufficient when extending it to real-world, heavily 3D-biased, applications. As such, in this project, I propose an alternative approach to the study of place cells in which a rat&rsquo;s neuronal activity is wirelessly monitored while it is allowed to freely explore a lattice maze in all directions of Cartesian space. Most importantly, I aim to show that receptive fields are of similar sizes in the horizontal and vertical directions; I also hypothesise that concatenating receptive fields (RFs) from several place cells will yield a layered organisation with inter-RF distances being larger in the x-z/y-z planes than the x-y plane. Incidentally, this study will also provide data&nbsp;which I hypothesise will confirm the horizontal bias model in murine behaviour proposed by Jovalekic et al. (2011).</p>
Amount: £0
Quantifying the activity of cis-regulatory sequences in the hypothalamus using single molecule fluorescence microscopy.
<p>Every cell in the nervous system contains a programme of gene expression that not only determines its morphology and function, but also allows neurons and circuits to respond and adapt to sensory experiences. It is well document that changes in gene expression in response to these stimuli require cis-regulatory DNA sequences (enhancers), which mediate the activation and repression of specific genes. However, how a neuronal network as a whole tunes their transcriptional responses to achieve behavioural changes remain elusive. This project aims to address this by examining how the regulation of the genes arginine vasopressin (AVP) and oxytocin (OT) (neuropeptides that play a role in mammalian social behaviours) can differ between neurons and even gender, by identifying how different enhancer elements contribute to cell-type specific expression. To do this we will combine an enhancer assay with RNA single molecule fluorescence in situ microscopy (smFISH) in the hypothalamus, where these genes are primarily expressed. This will allow us to quantify the activity of specific enhancers in a given context, such as cell type and gender. The results will therefore give an indication of how information is encoded within these enhancer sequences that allows specific expression of the AVP and OT genes.</p>
Amount: £0
Investigation of protein CoAlation in the process of apoptosis
<p>CoAlation is a novel post-translational modification to proteins whereby Coenzyme A is covalently attached to proteins. It occurs as part of the oxidative stress response as an alternative mechanism to protein glutathionylation. It is specifically a modification of enzymes involved in cellular metabolism and protects catalytic thiol groups on active site cysteine residues from irreversible damage by reactive oxygen species and reactive nitrogen species.&nbsp;</p> <p>&nbsp;</p> <p>Applying oxidizing agents to cells results in induction of apoptosis. Such agents also induce protein CoAlation. The aims of this project are to monitor induction of apoptosis in HEK293 cells in response to treatment with oxidizing agents using anti-PARP3 and anti-Caspase 3 Western blot and Fluorescence-activated Cell Sorting and to analyse the pattern of CoAlation at different stages of apoptosis using anti-Coenzyme A Western blot.</p>
Amount: £0
Developing gene therapy for the inherited childhood epilepsy, Dravet Syndrome
<p>Dravet syndrome is a rare, incurable epilepsy which affects young children. Before two years of age they have seizures, incoordination and cognitive impairment. They carry mutations in the SCN1A gene, which codes for voltage-gated sodium channel Na<sub>V</sub>1.1. This protein is expressed in hippocampal inhibitory interneurons.</p> <p>&nbsp;</p> <p>Gene therapy offers several advantages over conventional drugs. It is a treatment which targets the cause of the disease by delivering the corrected copies of the SCN1A directly to brain cells.</p> <p>&nbsp;</p> <p>Our hypothesis is that we can incorporate a promoter to achieve persistent expression specifically in inhibitory interneurons of the hippocampus. We aim to compare two novel promoters against a pan-neuronal promoter, synapsin. The first is a truncated endogenous promoter, Gad67. The second is a synthetic promoter identified by <em>in silico</em> analysis.</p> <p>&nbsp;</p> <p>Before the&nbsp;project commences, we will clone these two promoters into lentiviral vectors. These, and a synapsin vector, will be injected intracranially into neonatal mice.&nbsp; At the start of the project the brains from four mice will be co-stained with antibodies directed against GFP and inhibitory interneurons to assess colocalisation. To measure persistence of expression from these promoters, the four remaining mice will be subject to whole-body bioluminescence imaging twice-weekly.</p>
Amount: £0
Optimisation of carrier materials for the delivery of olfactory ensheathing cells in spinal cord injury
<p>Transplant-mediated repair is a promising method in spinal cord injury (SCI) treatment. This&nbsp;involves transplanting therapeutic cells that promote nerve regeneration at the site of injury. For SCI, one promising&nbsp;therapeutic cell type is olfactory ensheathing cells (OECs). These&nbsp;have been shown to remyelinate demyelinated axons and promote new synapses following injury. They are also easily accessible clinically via trans-nasal endoscopic biopsy, and compelling pre-clinical evidence means that they are now close to being formally tested as part of a first-in-man clinical trial. However, currently these cells are delivered as a simple cell suspension, and&nbsp;this is unlikely to be optimal for creating a permissive and optimised&nbsp;repair environment.&nbsp;</p> <p>Thus, the objective of this project will be to develop and engineer optimised&nbsp;biomaterial scaffolds for OEC delivery.&nbsp;In&nbsp;doing so, it is hoped that a permissive 3D extracellular environment can be created, and the phenotype and behaviour of OECs&nbsp;optimised for spinal cord repair. Promising prospective biomaterials include fibrin, collagen and collagen-fibrin blends. To this end,&nbsp;we will investigate the effect of&nbsp;these&nbsp;promising carrier materials on&nbsp;OEC survival and phenotype, particularly with a focus on changes they may cause on 3D cell morphology.</p>
Amount: £0
Developing a behavioural task for measuring the ability of listeners to perform auditory scene analysis.
<p>The auditory brain separates simultaneous sounds arriving at the ear into identifiable and localisable sources by a process known as Auditory Scene Analysis (ASA). The two steps that are involved in ASA are i) segregation of the simultaneous auditory information and ii) the integration of the sounds from the same source into one stream. To understand how these two steps are connected and how different auditory cues interact to shape the scene, this project will develop a behavioural task and analyse the performance of human listeners. A target vowel will be presented alongside with a distractor vowel, and human listeners will identify what the target is. Listeners will only be able to identify the target if they can separate the two sounds: changing the location and pitch of target and distractor will help this. In order find out whether the separation of competing sounds is facilitated by the formation of perceptual streams, the vowels will also be presented as part of a sound sequence. Our hypothesis is that the ability to identify a target vowel will be improved by the formation of two perceptual streams. The long-term goal is to develop a behavioural paradigm suitable for humans and animals.</p>
Amount: £0
Up and down regulation of MafB gene in the developing chick hindbrain.
<p>The project's aim is to up and down regulate MafB gene, that is expressed in the Nucleus Laminaris (NL) and Nucleus Angularis (NA), in the&nbsp;developing&nbsp;chick hindbrain and ask questions about:</p> <p>1) formation of nucleus Laminaris&nbsp;and nucleus Angularis&nbsp;in the dorsal&nbsp;hindbrain;</p> <p>2) other effects&nbsp;on hindbrain development e.g interfering with fgf8 molecule expression, which in turn would affect the development of the cranial motor nerves VI, VII and nVIa.</p> <p>Such experimental techniques as <em>in </em><em>ovo</em>&nbsp;electroporation, immunofluorescence and <em>in situ</em> hybridization will be used to look at the genes expressed in the auditory brainstem.&nbsp;The<em> in </em><em>ovo</em><em> </em>electroporation&nbsp;constructs used will overexpress&nbsp;MafB and also express a dominant negative version of MafB and immunofluoresce&nbsp;analysis will be carried out to test whether the electroporation was successful. The <em>in situ </em>hybridization analysis will be performed to establish the effect of MafB on the expression of such genes like FGF8, Pou6F2, N-cadherin, gamma catenin, cadherin-13 and cadherin-22 in the hindbrain. These techniques would also allow the analysis of the formation of the nucleus Laminaris&nbsp;in the developing hindbrain.</p>
Amount: £0
Identifying Integrative and Conjugative Elements using DLIGHT
<p>Integrative and conjugative elements (ICEs) are mobile genetic elements present in both gram-positive and gram-negative bacteria. They mostly reside in the host chromosome and under certain conditions, will excise and transfer to a new host via the conjugation machinery. ICEs have been found to provide the host with a wide range of phenotypes, including antibiotic and heavy metal resistance and the ability to colonise a eukaryotic host, promote virulence and biofilm formation. The ability of ICE to spread to different species of bacteria through horizontal gene transfer is a major factor in bacterial evolution. Bioinformatics approaches have been increasingly used to identify possible ICEs through sequence similarity. In this project, we aim to find out the effectiveness of using an algorithm, DLIGHT (Distance Likelihood based Inference of Genes Horizontally Transferred) that was originally used to detect lateral gene transfer, to identify integrative and conjugative elements. We will achieve this by assessing DLIGHT's ability to recover already documented ICEs. We will also use DLIGHT to test certain sequences which we suspect to contain ICEs. The predictions of new ICEs will then be vetted through manual analysis and collaboration with experimentalists.</p>
Amount: £0