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Results

Homicide Specialist Support 01 Apr 2016

To provide specialist counselling support to people bereaved by homicide prior to 2010

Amount: £20,000
Funder: Ministry of Justice
Recipient: Cruse Bereavement Care

Grant to Oxfordshire Cruse Bereavement Care 12 Feb 2015

Funding awarded to contribute towards the initial start up costs to establish a bereavement support service in three hostels for the homeless.

Amount: £1,700
Funder: Oxford City Council
Recipient: Oxfordshire Cruse Bereavement Care

Volunteering Matters 06 Nov 2014

Piloting Engage and Transform, a scheme to break down cultural barriers and develop a long-term partnership of mutual benefit between public and social sector organisations.

Towards a unifying mechanistic picture of glycation-induced crosslinking of protein 06 Sep 2018

<p>Non-enzymatic glycation of protein leads to ternary crosslinks involving reducing sugars, lysine and arginine residues (e.g. glucosepane, pentosidine, and DOGDIC), which alter the physical properties of long-lived fibrous tissue and are strongly correlated with the severity of diabetes in individuals. However, it remains unclear whether there is a causal link between these crosslinks and microvascular complications of diabetes. Furthermore, the mechanism by which initial adducts between glucose and lysine (Amadori products) are transformed into highly reactive intermediates that lead to crosslinking is poorly understood. With experiments employing <sup>2</sup>H and <sup>13</sup>C-labelled glucose, novel synthetic reagents, HPLC/MS analysis and DFT computation, we intend to describe, in great molecular detail, the origin of advanced glycation end-products (AGEs) derived from lysine, arginine and glucose. In particular, we will test the hypothesis that a hitherto unexplored through-space 1,5-hydrogen shift and the catalytic role of protein environment is pivotal in determining the fate of the Amadori product. The results will form the basis of a larger collaborative programme that will predict sites on fibrous tissue where crosslinks are likely to form, and develop well-defined protein platforms for both exploring RAGE/lectin activation and identifying antibodies and small molecules as biological probes and therapeutic agents for diabetes.</p>

Amount: £100,388
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Re(al) Productive Justice: Gender and Disability Perspectives 30 Jul 2018

<p>The key goal of this project is to make visible the experiences of disabled people in Ireland seeking reproductive justice. This is a live political issue in Ireland at present, as many disabled activists have criticised the reliance by campaigners on disability as a ground for restricting or expanding abortion access. Given Ireland&rsquo;s changing stance on these issues, this is a critical time to secure the meaningful involvement of disabled people in reproductive justice reform. This project will achieve its goal using three complementary approaches. First, it will critically analyse the legislative and policy frameworks regulating reproductive decision-making for disabled people in Ireland in light of human rights norms. Second, it will use an oral history methodology to document the lived experience of disabled people in making reproductive choices in Ireland. Finally, it will draw on the findings from the legislative analysis and oral histories to develop a toolkit for health and social care practitioners. This toolkit will clearly outline the applicable legal regulation of this field in a manner accessible to practitioners, and document the supports which could be used to ensure respect for the reproductive rights of disabled people in health and social care decision-making processes.</p>

Amount: £812,835
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

The mechanisms that induce dedifferentiation to drive regeneration in the absence of stem cells 10 Apr 2018

<p>Cell fate stability maintains functionality and counteracts malignancy in complex organisms. However, lack of exit gateways from the differentiated state impedes regeneration in mammals. Other animals regenerate by allowing differentiated cells to dedifferentiate, making progenitors to replace lost cells; however, the mechanisms that induce reprogramming are unknown. Based on our preliminary results we hypothesize that senescent cells can provide a signal instructing neighboring cells to exit the differentiated state and regain stemness under specific circumstances. Hence, this project's primary objective is to identify the nature of this signal and the context in which it operates. We will use <em>Hydractinia</em>, a highly regenerative invertebrate model animal in which reprogramming to pluripotency occurs naturally; <em>Hydractinia</em> is genetically tractable and optically translucent, uniquely allowing in vivo experiments. Our specific aims are (1) to characterize the transcriptome, epigenome and developmental potential of the animal's stem cells; (2) to identify the factors that cause differentiated cells to reprogram and become stem cells; (3) to dissect the transcriptional network acting during natural cellular reprogramming. This research will provide novel information on how cell fate is kept stable, and what are the mechanisms that allow non-malignant destabilization of cell fate to regain plasticity and contribute to regeneration.</p>

Amount: £946,728
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Primary cilia and cellular senescence 05 Sep 2017

<p>Somatic cells undergo senescence after a finite number of divisions, indefinitely arresting their proliferation.&nbsp; The mechanisms of cellular senescence are not well understood, although DNA damage signalling is one major cause.&nbsp; We have found that senescent human fibroblasts have increased frequency and length of primary cilia, antenna-like structures that sense and transduce various extracellular signals, notably Hedgehog.&nbsp; Here we propose to test the hypothesis that primary ciliation contributes to cellular senescence.</p> <p>We will use genome editing in primary cells to ablate <em>CEP164</em>, which is required for primary ciliogenesis, and then follow the kinetics of cellular senescence in the knockout population. &nbsp;We also propose to examine cilium-controlled signalling pathways to determine how they are affected during the initiation of senescence programmes. &nbsp;We will perform competitive co-culture experiments between ciliated and non-ciliated populations to define how ciliation capacity directs senescence in mixed populations.&nbsp; Together, the proposed experiments will test a novel cellular mechanism of senescence, a process of great significance in human health and the normal aging process.</p>

Amount: £102,335
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Evaluating the combination of Oncotype DX and Neutrophil/Leukocyte Ratios as prognostic indicators of chemotherapy response in breast cancer. 27 Apr 2017

<p>This research will study the effect of the individual&rsquo;s immune system on their reoccurrence of breast cancer after chemotherapy. This would be a correlation between the Neutrophil to Lymphocyte Ratio (NLR) and the Oncotype Dx score. Previous research (unpublished) has demonstrated the significance of the NRL in predicting breast cancer outcomes in HER 2 overexpressing and Luminal B breast cancer (accounting for approx. 20% of all breast cancers). We will extend our previous research to include all four cancer subtypes (Luminal A and Triple negative breast cancer). We aim to compare the immune system&rsquo;s reaction to chemotherapy across all four cancer subtypes. A key goal is to determine if NLR predicts outcome or survival in Luminal A or TNBC. A further key goal is to determine if there is any predictive value of combining the NLR with Oncotype scores (in relevant cases).</p>

Disease-specific quality of life in children with suppurative otitis media, including children with Down Syndrome and Autistic Spectrum Disorder 27 Apr 2017

<p>Acute otitis media (AOM) is a bacterial or viral infection of the middle ear which may accompany an upper&nbsp;respiratory tract infection. AOM can occur at any age, however, it is most common between 3 months and 3 years old. At this age, the&nbsp;Eustachian tube is structurally and functionally immature.&nbsp;Diagnosis of AOM is made by clinical and physical examination with an&nbsp;otoscope. Otoscopic examination can show a bulging, erythematous tympanic membrane with indistinct&nbsp;landmarks and displacement of the light reflex.&nbsp;The treatment for AOM are analgesics such as paracetamol or ibuprofen and many cases resolve&nbsp;spontaneously. Antibiotics are frequently given. Antibiotics relieve symptoms quicker and may reduce the chance of&nbsp;residual hearing loss and labyrinthine or intracranial sequelae. With the emergence of antibiotic resistant&nbsp;organisms, it is recommended that a round of antibiotics be administered only for children at highest risk or for&nbsp;those with recurrent acute otitis media(RAOM). RAOM is defined as four or more episodes of AOM in a 6 month&nbsp;period.&nbsp;The aim of this project is to investigate the impact on the quality of life of children that present with recurrent&nbsp;acute otitis media(RAOM).</p> <p>&nbsp;</p>

Haemocompatibility and biocompatibility of a polyurethane-based polymer for use in prosthetic heart valves 27 Apr 2017

<p>Developing valves with efficient function and long-term durability without the need for anticoagulation therapy,<br> coupled with the ability to be accommodated in many different types of patient, are the principal requirements of<br> replacement heart valves. The current treatment options available do not fit well with these critieria.&nbsp;The overall aim of the project is to develop a biomimetic polymer alternative to pericardium heart valve leaflets with a more repeatable, consistent and predictable production process.</p> <p>&nbsp;</p> <p>Main research objective: To investigate the haemocompatability of the polymer valve. That is, to measure the<br> blood's response to contact with the valve by measuring parameters such as thrombogenicity, activation of<br> coagulation, blood cell countsand platelet activation.<br> Secondary research objective: To carry out a comprehensive collaborative literature review with my supervisor<br> to deisign an experiment that helps us to understand the blood's response to the polymer in a dynamic<br> environment i.e. simulating the in vivo scenario of blood being pumped across the valve and therefore coming in<br> contact with the valve while under stress. Time allowing, we will then carry out this experiment.</p> <p>&nbsp;</p> <p>We hypothesize that the polyurethane-based material will have equivalent haemocompatibility to that of a<br> commercially available aortic heart valve replacement.</p>

Functional characterisation of excitatory neurons 27 Apr 2017

<p>Autism spectrum disorder (ASD) is a complex, neurodevelopmental disorder characterised by deficits in social and communication skills, language delay and repetitive or stereotypical behaviour. A variety of copy number variations&nbsp;have been identified that play a role in&nbsp;ASD, including the Neurexin1 gene (NRXN1) which encodes a family of presynaptic cell adhesion transmembrane proteins, vital for neurotransmission and synapse differentiation. It is widely accepted that neurexin and mutations disturb the balance between excitatory (&alpha;- and &beta;-nrxn) and inhibitory (mainly &alpha;-isoform) synaptic activity&nbsp;that is thought to be critical in the pathology in ASD. The seminal discovery that somatic cells can be reprogrammed to produce induced pluripotent stem cells (IPSCs) has revolutionised biological research and medicine. The ability to differentiate these IPSCs into neural cells offers a tremendous opportunity to study disease modelling associated with impaired neuronal cell biology. In this study we will characterise the functional firing properties of IPSc derived glutaminergic neurons differentiated from normal controls and patients carrying a NRXN1 mutation. Functional properties will be assessed by patch clamp examining voltage gated sodium and potassium channels and action&nbsp;potential firing properties under current clamp conditions. This work will be essential to aiding our understanding of ASD.</p>

Biomaterial-enhancement of an ex vivo model of Parkinson’s disease 27 Apr 2017

<p>Parkinson&rsquo;s disease (PD) is&nbsp;a disorder of the aged and efforts at finding a cure have so far failed. In order to develop new therapies that halt or reverse the decline in brain function that occurs, researchers must find ways to better model the disorder in the lab. One approach makes use of organotypic rat brain slice cultures that retain many of the 3D features and properties of brains in vivo, but are easily manipulated in vitro. However, cultured slices often do not survive well and neurons of the substantia nigra pars compacta (SNpc), the main brain region implicated in PD pathology, are particularly vulnerable to culture conditions. The key aim of the proposed project is therefore to test the viability-enhancing properties of medium supplements, synthetic (poly(dimethylsilane), poly(glycolic acid), poly(lactic acid) and poly(vinyl chloride), poly(lactic-co-glycolic acid) and natural (collagen, hyaluronic acid, laminin, fibronection, fibrin, gelatin, chitosan, other brain extracellular matrix proteins) polymers. Cultured tissue viability will be monitored using LDH, MTT, live-dead assays, as well as immunohistochemical detection of the dopamine neuron marker tyrosine hydroxylase. The project will be carried out in the FitzGerald lab, within the Centre for Research in Medical Devices (C&Uacute;RAM) at NUI Galway.</p>

Effect of Cholinergic Neurotransmission Challenge on Emotion-Related Attention in Bipolar Disorder 27 Apr 2017

<p>A low dose of the acetylcholinesterase inhibitor, physostigmine will be used to challenge the cholinergic system while performing a functional MRI task of emotion inhibition in psychiatrically healthy participants and euthymic subjects with bipolar disorder. Prior to and immediately following the infusion of physostigmine, subjects will perform behavioural tasks of attention as well as rate their mood using the profile of mood states (POMS) and visual analogue scale (VAS) rating scales. The proposed project will assess an effect of cholinergic system challenge on mood and cognition and will compare effects between control and bipolar&nbsp;groups as well as across the cholinergic muscarinic type-2 receptor genotype (CHRM2 rs324650). We hypothesize that 1) the dose involved will not demonstrate measurable effects on mood, 2)&nbsp;will have&nbsp;detectable effects on performance of the task of emotion inhibition, and&nbsp;3) the latter effect will&nbsp;be more pronounced in those of the genotype (TT) associated with reduced autoreceptor (M2) concentrations (the brakes on cholinergic neurotransmission). The findings of the project will feed into a larger analysis of the activation patterns associated with attention and performance of the task of emotion inhibition and their changes following challenge of the cholinergic system.&nbsp;</p>

Effect of NRXN1 gene deletion on neurite outgrowth and cell fate in human induced pluripotent stem cells derived from ASD patients 27 Apr 2017

<p>Autism is a devastating neurodevelopmental disorder with unmet clinical needs. Multiple genetic factors are involved, and <em>NRXN1</em> is one of&nbsp;the most common rare but significant factors. Professor Shen at NUIG&nbsp;has been granted a SFI Investigator&rsquo;s award to investigate autism using induced pluripotent stems cells (iPSCs). They have derived iPSCs from controls and autistic patients with <em>NRXN1</em> deletions, and differentiate iPSCs into astrocytes and neurons. RNA sequencing data from 100 days of differentiated cultures demonstrated a disturbed balance of neurons and astrocytes in patients' samples. This project will therefore investigate if <em>NRXN1</em> deletion affects early birth of cell types. I will perform lineage differentiation protocol to directionally differentiate iPSCs into cortical lineage. I will compare proliferation in neural stem cells, and quantify their rates between patients and controls. I will investigate astrocyte/neuronal lineage determination using Tuj1 and GFAP markers. Autism symptoms appear early postnatally which correlates with development of neuronal network, and preliminary data showed dysregulation of MAPK and GSK3&beta; in patient neural stem cells, which play important roles in neurite outgrowth. I will therefore also investigate neuritogenesis during early neuronal differentiation. This internship is anticipated to provide evidence into how <em>NRXN1</em> deletion may affect autism-related early brain development.</p>

Analysis of H2AX protein abundance in human breast cancer cells 27 Apr 2017

<p>The integrity and stability of the genetic information&nbsp;is essential to life, however, DNA&nbsp;is continuously being damaged, either as a result of normal cellular processes or via the environment. Each cell receives thousands of DNA lesions per day and&nbsp;if these lesions are not repaired,&nbsp;or are repaired incorrectly, they can lead to mutations&nbsp;that can threaten cell or organism viability and ultimately cause cancer. In order to detect and repair the various forms of DNA damage, cells have developed a mechanism known as the DNA damage response. This project aims to better understand the role of an important protein component of the DNA damage response, H2AX, in breast cancer.&nbsp;</p> <p><br> We aim to measure H2AX protein&nbsp;abundance&nbsp;in several&nbsp;breast cancer cell lines and&nbsp;to&nbsp;identify if there is a link between the abundance of H2AX in breast cancer patients with different disease subtypes, such as luminal or&nbsp;basal/triple-negative.&nbsp;H2AX expression and protein abundance is potentially an important biomarker for breast cancer and here we aim to optimise methodologies so that&nbsp;small samples taken at biopsy&nbsp;can be measured. Furthering our knowledge of&nbsp;the DNA damage response in cancer cells is important to understand disease progression and treatment.</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p>

Microanatomy of the thumb carpometacarpal (1CMC) joint. 27 Apr 2017

<p>The 1CMCjoint&nbsp;is&nbsp;the joint in the hand most affected by osteoarthritis.However there&nbsp;is only limited information available on its microscopic structure, and the studies which have been performed are difficult to compare as they all utilise different techniques(CT, MRI, SEM).In work as yet unpublished (Wilkins) it demonstrated the feasibility&nbsp;of obtaining&nbsp;joints and imaging&nbsp;them by eSEM&nbsp;to give high resolution surface maps of the articular surfaces, comparable to those obtained in standard SEM.This project was commenced to attempt to integrate and correlate information from several of these techniques. The joints were then reprocessed for routine paraffin histology and&nbsp;the appearance of the joint surface correlated with the morphology of the articular cartilage and subchondral bone in histological sections.This is the first time that direct correlation of the joint surface with joint histology has been demonstrated.This project&nbsp;aims to extend these studies to include micro CT in the examination sequence.Radiographic and CT imaging are clinically useful in assessing joint disease. On successful completion this will enable direct correlation of clinically relevant imaging data with high resolution views of the joint surface and the cartilage bone interface.</p>

Family Factors and Psychosis 27 Apr 2017

<p>My research will focus on individuals that have been diagnosed with schizophrenia, bipolar disorder</p> <p>or schizo-affective disorder.&nbsp;The hypothesis which I will test in this research is that poorly functioning families, alongside families with high expressed emotion,&nbsp;are a prognostic factor in the<br> course of schizophrenia, bipolar disorder and schizoaffective disorder and are linked with the development of<br> psychotic episodes&nbsp;as a symptom of these disorders. I aim to investigate the correlation of the severity of the illness with the level of dysfunction within the family and establish what specific changes can be made in the family system<br> to serve as protective factors and hence improve patient outcomes. I also hope to identify which family styles are<br> protective to patients' mental health and are associated with the best patient outcomes and how the family perspective on mental health impacts on the health and recovery of patients.&nbsp;</p> <p>I will&nbsp;ask patients and families to fill in suitable&nbsp;questionnaires &nbsp;and I will analyse the data collected to come to evidence based conclusions.I will complete the project by undertaking a cohort study with baseline data collection of patients and family members.</p>