Dublin, Ireland

RCSI , is an elite Dublin-based medical institution, situated on St. Stephen's Green. The college is one of the five Recognised Colleges of the National University of Ireland. The college dates back to 1784 and at present incorporates schools of medicine, pharmacy, physiotherapy and nursing, providing both undergraduate and postgraduate levels of medical education.Among medical institutions outside Ireland, the use of the term "Royal College" currently indicates an oversight body for postgraduate medical education. RCSI performs such a function, but it is unique among the four Royal Colleges of Surgeons in that 100 years after its establishment, an undergraduate medical school was founded and this is now Ireland's largest medical school with over 3000 students from 60 countries. The RCSI is a sister institute of the Royal Surgical Colleges of the United Kingdom . Wikipedia.


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Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: WATER-5c-2015 | Award Amount: 3.57M | Year: 2016

The WHO estimates that in 2015 in Africa ~156 million people relied on untreated sources for their drinking water. WATERSPOUTT will design, develop, pilot and field-test a range of, sustainable point-of-use solar disinfection (SODIS) technologies that will provide affordable access to safe water to remote and vulnerable communities in Africa and elsewhere. These novel large-volume water treatment SODIS technologies will be developed in collaboration and consultation with the end-users, and include: 1. HARVESTED RAINWATER SODIS SYSTEMS for domestic and community use. (South Africa, Uganda). 2. TRANSPARENT 20L SODIS JERRYCANS. (Ethiopia) 3. COMBINED 20L SODIS/CERAMIC POT FILTRATION SYSTEMS. (Malawi) These are novel technologies that will create employment and economic benefits for citizens in both the EU and resource-poor nations. WATERSPOUTT will use social science strategies to: a. Build integrated understanding of the social, political & economic context of water use & needs of specific communities. b. Examine the effect of gender relations on uptake of SODIS technologies. c. Explore the relevant governance practices and decision-making capacity at local, national and international level that impact upon the use of integrated solar technologies for point-of-use drinking water treatment. d. Determine the feasibility & challenges faced at household, community, regional and national level for the adoption of integrated solar technologies for point-of-use drinking water treatment. WATERSPOUTT will transform access to safe drinking water through integrated social sciences, education & solar technologies, thus improving health, survival, societal well-being & economic growth in African developing countries. These goals will be achieved by completing health impact studies of these technologies among end-user communities in Africa. Many of the consortium team have worked for more than 15 years on SODIS research in collaboration with African partners.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-21-2016 | Award Amount: 6.00M | Year: 2017

In sub-Saharan Africa 95% of the population has no access to surgical services. In this region surgery a proven and often life-saving intervention is only accessible to urban populations, with only one surgeon per 2.5 million people in rural areas. Emerging evidence demonstrates that major surgery can be undertaken safely and effectively at district hospitals, making it accessible to otherwise neglected rural populations. Objectives: Guided by a health systems-strengthening framework and a comprehensive programme of research, Scaling up Safe Surgery for District and Rural Populations in Africa will scale up the delivery of accessible, elective and emergency surgery at district hospitals to national level programmes in three African countries: Malawi, Zambia and Tanzania. How objectives will be achieved: SURG-Africa is a tested intervention, drawing lessons from two large-scale successful interventions coordinated by members of this SURG-Africa consortium (one FP7 EC funded) that have trained and supervised non-physician clinicians to deliver essential and emergency surgery in four African countries. Platformed on comprehensive surgical systems analyses, it will put in place national surgical information systems; and will test innovative interventions for making specialist supervision of district surgery feasible and affordable. Epidemiological, economics and implementation research will evaluate impact, and provide evidence for policymakers. SURG-Africa directly addresses all aspects of Topic SC1-PM-21-2016: Implementation research for scaling- up of evidence based innovations and good practice in Europe and low and middle-income countries. The results will be transferable and scalable national surgical systems models, with implications for national budget factored in, for making safe surgical services accessible, equitable and sustainable in Africa, especially for women in rural areas.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.65M | Year: 2015

Endoplasmic reticulum (ER) stress is emerging as a common feature in the pathology of numerous diseases including cancer, neurodegenerative disorders, metabolic syndromes and inflammatory diseases. Thus ER stress represents a potential therapeutic intervention point to be exploited to develop novel therapies, diagnostic tools and markers for these diseases. However, exploitation is hampered by the shortage of scientists with interdisciplinary training that can navigate with ease between the academic, industrial and clinical sectors, and that have the scientific and complementary skills, together with an innovative outlook, to convert research findings into commercial and clinical applications. This proposal will bring young researchers together with world-leading academics, clinicians and industry personnel, who are united in (1) their goal of forming a network of excellence aimed at understanding the ER stress response mechanistically and quantitatively and (2) applying this understanding to identify and validate the most suitable intervention points in order to provide innovative knowledge-driven strategies for the treatment of ER stress-associated diseases. The TRAIN-ERS network will provide early stage researchers (ESRs) with high quality scientific and complementary skills training combined with international, intersectoral work experience. This will produce highly trained, innovative, creative and entrepreneurial ESRs with greatly enhanced career prospects, who will continue to advance the state of the art in the Biomedical field in their further careers, and will confidently navigate at the interface of academic, clinical and private sector research. The TRAIN-ERS research programme will provide the ESRs with the knowledge and the cutting edge scientific and technical skills that will drive our understanding and exploitation of the ER stress response for therapeutic and diagnostic purposes.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NMP-10-2014 | Award Amount: 8.83M | Year: 2015

Diabetes mellitus is a chronic disease characterised by high blood glucose due to inadequate insulin production and/or insulin resistance which affects 382 million people worldwide. Pancreatic islet transplantation is an extremely promising cure for insulin-sensitive diabetes mellitus (ISDM), but side effects of lifelong systemic immunosuppressive therapy, short supply of donor islets and their poor survival and efficacy in the portal vein limit the application of the current clinical procedure to the most at-risk brittle Type I diabetes (T1D) sufferers. The DRIVE consortium will develop a novel suite of bio-interactive hydrogels (-Gel) and on-demand drug release systems to deliver islets in a protective macrocapsule (-Shell) to the peritoneum with targeted deposition using a specialised injection catheter (-Cath). Pancreatic islets will be microencapsulated in -Gels; biofunctionalised injectable hydrogels containing immunosuppressive agents and polymeric microparticles with tuneable degradation profiles for localised delivery of efficacy cues. These -Gels will be housed in a porous retrievable macrocapsule, -Shell, for added retention, engraftment, oxygenation, vascularisation and immunoprotection of the islets. A minimally invasive laparoscopic procedure (O-Fold) will be used to create an omental fold and at the same time deliver -Shell. An extended residence time in -Gel will enhance long-term clinical efficacy of the islets and result in improved glycemic control. The novel -Gels will also be developed as human three-dimensional in-vitro models of in-vivo behaviour. Islet harvesting and preservation technologies will be developed to facilitate their optimised yield, safe handling and transport, and ease of storage. DRIVE will also enable the future treatment of a broader range of T1 and insulin-sensitive T2 diabetics by working with induced pluripotent stem cell experts to ensure the compatibility of our system with future stem cell sources of -cells.


Docherty J.R.,Royal College of Surgeons in Ireland
Cellular and Molecular Life Sciences | Year: 2010

In this review, subtypes of functional α1-adrenoceptor are discussed. These are cell membrane receptors, belonging to the seven-transmembrane- spanning G-protein- linked family of receptors, which respond to the physiological agonist noradrenaline. α1-Adrenoceptors can be divided into α1A-, α1B- and α1D-adrenoceptors, all of which mediate contractile responses involving Gq/11 and inositol phosphate turnover. A fourth α1-adrenoceptor, the α1L-, represents a functional phenotype of the α1A-adrenoceptor. α1-Adrenoceptor subtype knock-out mice have refined our knowledge of the functions of α-adrenoceptor subtypes, particuarly as subtype-selective agonists and antagonists are not available for all subtypes. α1-Adrenoceptors function as stimulatory receptors involved particularly in smooth muscle contraction, especially contraction of vascular smooth muscle, both in local vasoconstriction and in the control of blood pressure and temperature, and contraction of the prostate and bladder neck. Central actions are now being elucidated.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-IF-EF-RI | Phase: MSCA-IF-2015-EF | Award Amount: 187.87K | Year: 2016

Evidence is emerging that rapid, profound and persisting changes in gene expression regulation and post-transcriptional regulation underlies the epileptogenic process. The current proposal builds on preliminary data which demonstrates that rapid reduction of a microRNA; miR-124, causes increased expression and activity of NRSF, a master-regulator of epileptogenesis. The current proposal will build on this and investigate other gene networks regulated by miR-124 in neurons, by developing the first miR-124 KO mouse using CRISPR technology and a miR-124 overexpressing mouse. These transgenic mice will then be profiled at the epigenomic level using ATAC-Seq, the transcriptome level using HITS-CLIP and ribosomal profiling and the proteomic level using mass spec. This will be the first study to examine the pleiotropic role of miR-124 in mature neurons and identify gene networks regulated by this neuronally enriched miRNA. If miR-124 disruption causes aberrant activity of epigenetic modifiers including NRSF then we will test whether miR-124 restitution can restore correct gene expression networks and prevent or modify epileptogenesis in a mouse model of the disorder. Next we will determine whether data obtained in mouse models is translatable to the human form of the condition by obtaining and maintaining resected human epileptic hippocampus live in culture. We will ectopically introduce miR-124 and test the effect of miR-124 restitution on network activity and energetics using live-calcium imaging as well as the epigenomic and transcriptomic effects. Together this proposal represents the most in-depth analysis of miRNA function and will set the standard for future functional analyses of these molecules. Furthermore it has the potential to intervene in disease process and apply findings to a relevant human model providing a novel therapeutic target for the treatment of epilepsy.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 292.50K | Year: 2017

The aim of this project is to expand upon a newly discovered platform reaction by developing new routes to Active Pharmaceutical Ingredients (APIs) Tolterodine and Ezetimibe and other advanced intermediates for the manufacture of drugs (i.e. benzylic fluorides and alcohols). It is planned that this platform will serve to enhance the competitiveness of the European pharmaceutical manufacturing industry as it continues to face increased competition from other economies In order to achieve this aim we need to bring together expertise in (i) Organic Synthesis [Royal College of Surgeons in Ireland, RCSI] (ii) Enantioselective fluorination [Nagoya University Japan, Nagoya] (iii) Drug development and production [Integrated Research in Biotechnology & Medicine, IRBM] To meet the aim we have divided the project into the following work packages: WP1: Development of a new synthesis of Tolterodine. WP2: Scale up of synthesis of Tolterodine. WP3: Development of a new synthesis of Ezetimibe. WP4: Scale up of synthesis of Ezetimibe. WP5: Exemplification of alkoxylation to prepare enantiopure benzylic alcohols API intermediates WP6: Preparation of benzylic fluorides WP7: Management, Training, Dissemination & Communication


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-IF-EF-ST | Phase: MSCA-IF-2014-EF | Award Amount: 175.87K | Year: 2016

Glycoprotein therapeutics are widely seen as the next generation of drugs. 80% of new therapeutic drugs in phase 3 development are biologics. However, the early detection of critical glycosylation changes in biopharma pro-duction (i.e. in the drug producing cells) and the rapid and sensitive identification and separation of closely relat-ed protein-drug glycoforms presents an industry wide problem. This project aims to develop a low-cost and easy-to-produce glycopeptide separation platform. This will be based on highly porous polyHIPE structures obtained from fast and scalable polymerisation and subsequently functionalised with reactive groups. The latter will be employed in the conjugation with novel recombinant lectins that have very selective carbohydrate-binding prop-erties. The separation of closely related glycoproteins will be investigated. Moreover, the integration of the lectin conjugated porous polymers into a device format will be addressed. This is a highly interdisciplinary project at the interface of polymer and material science, biotechnology and separation science. The applicants diverse experi-ence in academic and industrially informed projects makes him an ideal match for this project. It provides a unique environment for the researcher to develop his skills supported by unique scientific and complementary training and accelerate his academic career in applied material science. The dissemination of research results will target the professional audience as well the general public through outreach activities.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-IF-EF-ST | Phase: MSCA-IF-2015-EF | Award Amount: 175.87K | Year: 2017

Cystic fibrosis (CF) is a hereditary disease involving a defective ion channel, resulting in altered epithelial cell function and consequent infective/inflammatory airway exacerbations. Progressive loss of lung function is the leading cause of death in CF patients. It is statistically noted that females have a disadvantage in survival and morbidity; this is commonly referred to as the CF gender gap. Recent studies have implicated the female sex hormone, estrogen, in this gender gap. CF patients show altered microRNA expression and some of the affected miRNAs are predicted to target genes encoding key inflammatory mediators such as Toll-like receptor 4 (TLR4) and tumour necrosis factor a receptor associated factor-6 (TRAF6). This highly innovative proposal, to be implemented at the Royal College of Surgeons Ireland (RCSI), aims to study the regulation of key miRNAs by estrogen and investigate if this plays a role in the CF gender gap. I will combine my own expertise in pulmonary innate immunity with the host PIs world-class knowledge of CF and miRNA research. The research will further our understanding of inflammation in CF to aid development of better therapies. I will develop professionally as I: a) diversify my competencies through the acquisition of new laboratory skills (e.g. qPCR, flow cytometry), b) strengthen my transferable skills (e.g. project management, public engagement, data dissemination) and c) expand my collaborative network through secondments to other world-renowned research teams in Leiden University Medical Centre, Netherlands and University of Heidelberg, Germany. I will contribute richly to research at RCSI as I am already equipped with skills applicable to ongoing work in the team and am keen to take an active role in student supervision. The opportunities carried by this fellowship will form the cornerstone of my career, accelerating my progression towards my goal of achieving a position of independence in respiratory immunology research.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-IF-GF | Phase: MSCA-IF-2015-GF | Award Amount: 248.06K | Year: 2016

Tissue engineered vascular grafts (TEVGs) hold great promise in the field of regenerative medicine and also possess the true potential to revolutionise the way in which clinicians treat the growing burden of cardiovascular disease. Treatment is achieved by incorporating an appropriate cell source onto a biodegradable scaffold and implanting the graft to bypass non-patent vascular segments. However, numerous issues regarding TEVG cell source render the technique unviable in a clinical setting as the cells require high levels of manipulation including digestion, isolation and culture. These issues increase processing costs, decrease cell stability and raise numerous regulatory issues. The use of minimally manipulated liposuction aspirate fluid (LAF) may offer a safer and more efficient cellular source in regenerative TEVGs. However, the capacity of LAF to act as a viable cell source for TEVGs is untested. The aim of this project is to determine the capacity of LAF derived cells to act as a viable cell source for TEVGs. This will be achieved through characterisation of the LAF cells, investigation of the environment that best promotes favourable cellular behaviour, an in vivo study on the viability of the graft to act as a vascular interposition in a small animal model, scaling of the graft to appropriate human size and finally an in vivo study of the grafts ability to function as a vascular bypass in a large animal model. This fellowship will have an outgoing phase to Prof David Vorps Lab at the University of Pittsburgh and a return phase to Prof Fergal OBriens Lab at the Royal College of Surgeons in Ireland. Having recently completed my PhD, which focused on the mechanical and morphological characterisation of human diseased vascular tissue, this fellowship will allow me to expand my existing repertoire of research and complementary skills to consolidate and build upon what I have learned to date as I evolve my independent, professional research career.

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