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Biomaterial-based delivery of neurotrophic factors to the Parkinsonian brain 31 May 2018

The concept of cellular brain repair for Parkinson's disease is relatively simple - if brain cells die in this condition, then it should be possible to replace these cells through transplantation of healthy cells back into the brain. Over the past three decades, numerous animal studies and several clinical trials in human patients have shown that this concept has significant potential for repairing the brain affected by Parkinson's disease. However, poor survival of the healthy cells has limited the widespread roll-out of this cellular reparative approach to patients. Biomaterials, that is, materials that have been engineered to interact safety with living tissue for therapeutic purposes, have the potential to improve such cellular reparative therapies for Parkinson's disease. Specifically, injectable biomaterials gels have the potential to significantly improve cell survival by providing a physical scaffold and pro-survival environment for the implanted cells. Thus the aim of this proposal is to determine if biomaterial hydrogels can be used to improve cellular reparative therapies for Parkinson’s disease using animal models of the condition. We will specifically investigate the beneficial effect of biomaterials on stem cell-derived neuron cell transplantation approaches.

Investigating acetylation control of MutSbeta protein (Msh2-Msh3) in DNA triplet repeat expansions. 31 May 2018

Huntington’s disease (HD) is a debilitating, relentlessly fatal neurodegenerative disease. HD is caused by inheritance of an expanded CAG repeat tract in the HTT gene. The CAG repeat continues expanding in the brain of HD patients, and these somatic expansions contribute to disease progression and age of onset. It is known from model systems that the DNA repair protein MutSbeta (Msh2-Msh3 complex) is essential to drive expansions, as knockout of either Msh2 or Msh3 blocks nearly all expansions. Recent work from the supervisor’s laboratory suggests that MutSbeta expansion activity is regulated by post-translational acetylation. This link to protein acetylation is noteworthy with regard to potential therapy, in light of the supervisor’s recent demonstration that inhibiting histone deacetylase 3 in HD mice blocked disease onset. Using cultured human cells, I will test potential acetylation control of the Msh2 subunit of MutSbeta by mutating a putative acetylation site, lysine 73, to convert it to the non-acetylatable arginine (Msh2K73R). I will then test Msh2K73R protein expression and its ability to form MutSbeta complex. I will assist in genetic assays to measure CAG repeat expansions in cells expressing Msh2K73R, compared to wild type. My prediction is Msh2K73R will drive expansions in an acetylation-independent manner.

Feasibility and acceptability of a decision aid to facilitate involvement of people with type 2 diabetes in decisions about medication intensification in an Irish setting 31 May 2018

The primary goal of this study is to assess the feasibility and acceptability of using the Diabetes Medication Choice Decision Aid in decisions about medication intensification in an Irish setting using a mixed methods approach. The extent to which patients are involved in the decision-making process about medication intensification will be measured using a validated tool (OPTION) in audio-taped consultations where the decision aid is used and not used. Health care professionals and patients will also be interviewed about how useful they found the decision-aid in involving patients in decisions about changes to medication.The quantitative analysis of the consultations will allow us to assess the level of patient involvement in the decision-making process around medication intensification. The qualitative interviews will provide us with a greater understanding of how useful the decision-making tool is in facilitating shared decision-making. The findings from this feasibility study will inform a future pilot randomised controlled trial of the decision aid in people with type 2 diabetes requiring medication intensification.

Investigating the genetic basis of schizophrenia and associated cognitive deficits 31 May 2018

Schizophrenia desperately needs new drugs. It affects 1% of adults, is a global health problem yet medications are only partially effective. They reduce psychotic symptoms but not negative symptoms and cognitive deficits, which are key factors for explaining illness-related disability. Schizophrenia and cognition are complex but highly heritable so genetics represents a vital tool for understanding neurobiology in the absence of biomarkers. A network of 150 coexpressed genes has been identified that is conserved throughout the human cortex. It is enriched for rare and common genetic variants associated with cognitive phenotypes and neuropsychiatric disorders. I plan to use the newest/largest available genetic studies of schizophrenia and cognition ( > 380,000 individuals) to study this gene network in these phenotypes. I will use gene-set analysis to test the network for enrichment of genes associated with schizophrenia or cognition. I will quantify the proportion of SNP-based heritability for schizophrenia or cognition that can be attributed to genes in this network. I will investigate what individual genes are associated with either phenotype or with both, i.e. genes that are having a pleiotropic effect. This can point to the biological processes that underlie cognitive deficits in schizophrenia and be a foundation for new methods of treatment.

Mitral Valve Reconstruction and Analysis 31 May 2018

Valvular heart disease (VHD) has been described as the ‘next cardiac epidemic’ with 6.5 million new cases of VHD predicted to develop in Europe by 2050. Mitral regurgitation (MR) accounts for 32% of VHD. MR is a condition where the native valve leaflets do not fully close, resulting in backward blood flow from the left ventricle to left atrium. Image-based computational predictive models have excellent clinical potential as an assessment strategy for cardiac devices treating mitral valve dysfunction. However, these computational models are limited. They assume idealised healthy conditions, and often lack validation from human imaging. The project will involve analysing CT (computed tomography) imaging of patients with healthy mitral function (e.g. patients presenting with aortic valve dysfunction) and then patients with mitral dysfunction, specifically mitral regurgitation. The 2D images will be reconstructed into 3D geometries and segmented to extract the mitral valve annulus and bicuspid leaflets, at both open and closed states. Following reconstruction, the geometries will be assessed and the effective orifice area when open will be analysed for healthy and diseased mitral valves. This project will demonstrate the change in leaflet structure with disease and will serve as input to ongoing work in Dr. Conway’s group.

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

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

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

The integrity and stability of the genetic information is essential to life, however, DNA 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 if these lesions are not repaired, or are repaired incorrectly, they can lead to mutations 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. We aim to measure H2AX protein abundance in several breast cancer cell lines and to identify if there is a link between the abundance of H2AX in breast cancer patients with different disease subtypes, such as luminal or basal/triple-negative. H2AX expression and protein abundance is potentially an important biomarker for breast cancer and here we aim to optimise methodologies so that small samples taken at biopsy can be measured. Furthering our knowledge of the DNA damage response in cancer cells is important to understand disease progression and treatment.

Knowledge, Attitude and Behaviours of Medical Students Towards Sexual Health 27 Apr 2017

Sexual health is a key component to a holistic approach to health frequently overlooked as quite a taboo subject. Medical students as future healthcare professionals and advocates of a healthy lifestyle, it is therefore critical that they understand the importance of their own sexual health and that of their future parents. As part of my research project I plan to investigate the knowledge attitudes and behaviours of undergraduate medical students around sexual health. Notably focussing on the areas of contraception, STI’s, sexual activity and how students feel their knowledge in these areas has been influenced by the medical curriculum. As well as this identifying where possible influential factors such as social, cultural, personal, economic and educational. This study will be carried out following extensive literary reviews in the areas, before compiling a questionnaire for distribution in a cross-sectional survey of undergraduate medical students. The results obtained will be entered into SPSS for cleaning and analyses. This data can then be used a comparison against both national and international based studies. Highlighting any new data. Finally dissemination of findings, via Wellcome Trust research report, conference presentation and peer reviewed journal article.

Diabetes Mellitus, Human Uterine Contractility and Labour 27 Apr 2017

It is well recognised that both maternal obesity in pregnancy, and maternal gestational Diabetes Mellitus (DM) result in a much greater need for caesarean section for delivery of the infant (1-3). There is an emerging view that the human uterine smooth muscle is subjected to some type of metabolic dysregulation in these conditions, but the exact factors involved are unknown. The aim of this project is to examine the effects of a number of biomarkers associated with DM in obese women on the contractility of human pregnant myometrium in vitro. The effects of glucose, Proinsulin C-Peptide, and Insulin, on spontaneous, and agonist (oxytocin)-induced contractions of human myometrium in vitro, obtained in the third trimester of pregnancy, will be examined. The following parameters will be measured, and compared with simultaneously run control experiments: frequency and force of contractions, peak amplitude and integrals of contractile activity over 15-minute periods. The raw data measured will be compared using ANOVA, followed by Tukey's HSD test for post-hoc analysis, with significance taken as a P value

The role of low dose chemotherapy in sensitising the colon tumour microenvironment to immunotherapy 01 Apr 2016

Metastatic colorectal cancer (CRC) is a lethal disease. Current therapies involve surgery, or palliative chemotherapy, comprising combinations of fluorouracil, oxaliplatin or irinotecan. While therapeutic interventions are beneficial, the overall prognoses for patients with CRC are poor. Therefore, new strategies to treat this problem are needed. Immunotherapies have potential for treatment of metastatic disease as they act through unrelated mechanisms. Recent data has shown that low-dose chemotherapy in combination with immunotherapeutic targeting using monoclonal antibodies can enhance tumour cell elimination by antibody-dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC). Using an established syngeneic in vitro model of colon cancer and immune effector assays, the aim of this project will be to investigate the effects of low dose chemotherapy, fluorouracil, 5FU, on overriding colon cancer induced immunosuppressive potential and activating innate effector functions in vitro. Preliminary data indicates that 5FU treatment of CT26 cells in-vitro induces PD-L1 expression on CT26 cells. Additionally, we have evidence that low dose 5FU treatment of CT26 cells induces co-cultured macrophage effector function in tumour cell clearance in vitro. We will investigate in vitro if treatment of CT26, colon cancer cells, with 5FU in the presence of anti-PD-L1 antibody will enhance ADCC/ADCP mediated tumour cell clearance by macrophages.

Attention Deficit Hyperactivity Disorder in Adults: Use of Eye-Tracker to Detect Attention Deficits 01 Apr 2016

Current diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) in adults is by subjective measures. Our project examines the value of diagnosis of adult ADHD by objective means through the use of an eye-tracking device. Therefore our proposed goals are: 1. To find out the prevalence of ADHD using subjective tests in those adults who attend the mental health services in Sligo/Leitrim County, Republic of Ireland2. To investigate the use of an objective test in the diagnosis of ADHD 3. To explore the use of the objective test to distinguish ADHD from its associated comorbid conditions. 4. The results will be disseminated through peer-review publications and at international and national conferences, but most importantly will lead to further studies in which interventions will be tested for their potential to enhance care, and reduce the levels of educational and employments dysfunction of people with adult ADHD symptomatology.

'From a source of shame to the pride of the Island:' Disability, Advocacy & the Media in Ireland, 1959-2003. 12 May 2015

This project will examine the treatment and perception of the disabled community in Ireland during the period 1959-2003. Its objectives are fourfold. First, to provide the first detailed history of disability/disability provision in Ireland in this period. Second, to examine how the perception of the disabled changed, from viewing disability as indicative of divine will (necessitating seclusion from broader society), to the view that state policy must show an awareness of the need for self-regul ation and autonomy for members of the Disabled Community. Third, to unravel the impact of those changes in the development of the Irish state's system of disability provision, as the duty of care increasingly shifted towards state mechanisms of support and care. This led to the introduction of new systems of care, provided by the state, including disability benefit and the carer's allowance, fundamentally changing the level of state intervention in their lives. Finally, to provide an insight int o how community integration became the standard mode of disability care and how the current system of state provision for the disabled came into being. Thus, the central research questions will be around what shaped and catalysed change to the care systems for the disabled in Ireland?

Amount: £81,095
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Cell explorers a model for sustainable public engagement by third level institutions. 11 Jul 2013

Cell EXPLORERS is an exciting science engagement programme linking university and primary schools. It is the only programme in the West of Ireland to promote biological and biomedical sciences through a practical biology programme. Cell EXPLORERS stimulates interest and excitement through discovery learning in school visits and interactive workshops. The success of Cell EXPLORERS relies on its novel way of bringing teams of volunteer students and researchers to engage with the public in pract ical activities. Cell EXPLORERS has run as a successful pilot project and has been chosen to integrate the science outreach and public engagement programme of the highly research active NUI Galway School of Natural Sciences. This new stage of development will enable sustainable public engagement within SNS, by integrating staff engagement and enabling undergraduate student participation in science education. The objectives of this project are: 1. To develop a model that engages un dergraduate Biochemistry students in biomedical science communication and generates sustainable public engagement tools. This will contribute to the training of the next generation of science ambassadors and science educators. 2. Support formal learning by delivering schools workshops and creating a teacher training programme in collaboration with the Galway Education Centre Further development of Cell EXPLORERS at a larger scale will allow its future integration in the undergraduate curricu lum and its potential use as a STEM promotion model within Ireland and the UK.

Amount: £29,987
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Assembly and function of Drosophila melanogaster centromeric chromatin during meiosis and development. 13 Nov 2012

Centromeres are key regions of eukaryotic chromosomes that ensure proper chromosome segregation at cell division. In most eukaryotes, centromere identity is defined epigenetically by the presence of a centromere-specific histone variant CenH3. How CenH3 is incorporated and reproducibly propagated during the cell cycle is key to understanding this essential epigenetic mechanism. Improper regulation of CenH3 assembly leads to hallmarks of cancer including the formation of extra centromeres, aberra nt segregation of chromosomes and aneuploidy. Recent studies in single cell eukaryotes or cultured cells have identified molecules critical for CenH3 assembly during the mitotic cell cycle, paving the way for investigations into the mechanisms that specify centromere identity, function and regulation in animals. Meiosis is an essential part of the reproductive cycle and chromosome segregation defects result in aneuploid eggs, sperm and resulting zygotes. However, in contrast to mitosis, the func tional requirements, cell cycle timing and regulation of CenH3 assembly in the specialised meiotic divisions are largely unknown. This proposal aims investigate the function and timing of CenH3 assembly during meiosis and early development in Drosophila melanogaster. A major goal is to uncover the contribution of centromeric chromatin to the maintenance of genome stability in meiotic and mitotic cells in multi-cellular animals.

Amount: £517,976
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Vacation biomedical scholarship 24 Jun 2013

Not available

Amount: £21,240
Funder: The Wellcome Trust
Recipient: National University of Ireland Galway

Grant to Volunteering Matters 20 Dec 2013

Great War pop-up exhibition

Amount: £9,700
Funder: The National Lottery Heritage Fund
Recipient: Volunteering Matters
Region: North East
District: County Durham

Women Against Sexual Exploitation and Violence Speak Up Project (WASSUP) 11 Dec 2017

To support the development of the WASSUP project.

Amount: £20,000
Funder: Suffolk Community Foundation
Recipient: Volunteering Matters

Volunteer Britain 14 Jul 2005

Community Service Volunteers (CSV) works to reconnect people to their community through volunteering and training and to enrich people?s lives. This project will produce short audio and visual clips on volunteer's experiences, produced by the volunteers themselves. CSV will showcase the clips in order to recognise their efforts and promote volunteering to others, through radio, TV and at local community events. This will be done in conjunction with the 'Year of the Volunteer' campaign.

Amount: £49,056
Funder: The Big Lottery Fund
Recipient: Volunteering Matters
Region: London
District: Islington London Boro

Lampton Community Gardens 15 Sep 2006

CSV Environment (Bristol) will promote and develop the community gardens and establish a volunteer community management group to sustain it for the benefit of all local residents.

Amount: £9,724
Funder: The Big Lottery Fund
Recipient: Volunteering Matters
Region: South West
District: City of Bristol