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Results

Ocular Drug Delivery by Using Preformed Biodegradable Implants 27 Apr 2017

Glaucoma can result in damage to the optic nerve and vision loss, which is a leading cause of blindness. Eye drops is the most commonly used treatment for glaucoma in clinic. This treatment is associated with low bioavailability of the applied drug and unpleasant side effects resulted from frequent administrations. This study aims to develop novel ocular drug delivery systems using drug-loaded biodegradable implants for the treatment of glaucoma. In this study, drug-loaded implants composed of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) will be formulated. The structure, thermal properties, mechanical properties, degradation behaviors and in vitro drug release profiles of the implants will be further investigated. These drug-loaded implants can provide a sustained release of the incorporated drug, reduce the burden of frequent administration and finally improve patient compliance.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Ocular Drug Delivery by Using Phase Invertible Implants 27 Apr 2017

Age–related macular degeneration (AMD) currently affects more than 600,000 people in the UK and is the leading cause of vision loss. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) is an effective treatment for AMD patients. However, frequent injections are required in the treatment, which is expensive and often associated with complications and poor patient tolerance. This study focuses on the development of novel ocular drug delivery using in situ forming implants to treat AMD. In this study, in situ formed implants composed of biodegradable polymers will be formulated using PLGA and biocompatible organic solvent. Various properties of the in situ forming systems will be investigated, such as thermal properties, rheological properties, degradation behaviors and in vitro drug release profiles. These in situ forming implants can sustain the release of incorporated drugs, reduce complications caused by frequent administration and ultimately improve patient comfort.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Immunomodulatory effect of cigarette- and electronic cigarette- exposed respiratory pathogens on macrophages in vitro 27 Apr 2017

It has been established that cigarette smoke and E-cigarette vapour can activate inflammatory response and impair antimicrobial functions of human immune cells. However, the direct effects of cigarette smoke and E-cig vapour on respiratory pathogens is less well known. The aim of this project is to further explore the effect of cigarette smoke extract (CSE) and e-cigarette smoke extract (ECSE) on important human respiratory pathogens and their interaction with the host. The immunomodulatory effects of CSE/ECSE exposed respiratory pathogens have on macrophages in vitro will be determined. Western blot analysis will be used to detect activation of the canonical NF-kappaB pathway and caspase-1 activation whilst ELISA assays will be utilized to measure the expression of the cytokines IL-8, IL-12, TNF-alpha and IL-1beta. In addition, susceptibility of bacteria to macrophage phagocytosis and killing will be measured. The findings of this project will provide valuable information about the direct effect of cigarette smoke and e-cigarette on the lung microbiome and its interaction with host immune cells.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Lignin-based hydrogels as an innovative solution to combat the global healthcare challenge of medical device-associated infections 27 Apr 2017

The proposed research involves investigation of the antimicrobial properties of zinc-loaded, lignin-based hydrogels as candidate infection-resistant medical device coatings to combat the escalating burden of device-associated infections. Lignin is the second most abundant naturally-occurring polymer globally and is also a major waste product of industrial processes, for example paper and bio-refinery industries. The rationale of this project is based on the ability of lignin-based hydrogels to absorb metallic cations, which are widely recognized for their broad-spectrum bacteriostatic and bactericidal activities, and consequently enhance the inherent, and recently reported, antimicrobial activity of lignin itself. Prevention of bacterial colonisation on implanted medical devices with the use of lignin-based hydrogel coatings is anticipated to have transformational impacts on patient health and would, additionally, represent an important mechanism of re-using this major industrial waste product. Key goals are to: Determine resistance of the novel materials to adherence of Proteus mirabilis and Staphylococcus aureus, representative Gram-negative and –positive nosocomial pathogens respectively. Characterise efficacy of eluted metallic cations, including zinc, in inhibiting growth of nosocomial pathogens. These findings will ultimately inform further development of these innovative, low-cost and environmentally-friendly materials as medical device coatings to combat the global healthcare challenge of device-associated infections.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Transformations: Encountering Gender and Science 16 Jun 2018

The Rethinking Sexology team’s historical research has uncovered important material on the relationship between medical authority and ‘patient’ experience and the development of diagnostic categories/treatment protocols. We propose a public engagement programme that invites young trans people (age 16-25) to explore this material, co-conduct new research, including an oral history project, and develop an ambitious programme of creative responses leading to a performance and exhibition in four relevant high-profile venues across the UK. The plan of action has been developed during an extensive consultation period with key stakeholders, in which ideas and methodologies have been fully tested. The programme is led by the Rethinking Sexology (RS) team who has an outstanding track record in field-leading engaged research and public engagement. The team’s experience will be complimented by collaborating with a uniquely qualified group of writers, performers and youth-facilitators, known for their pioneering and award-winning work with the trans community, with whom the RS team already has long-standing collaborative relationships. The programme will deliver a set of exceptionally innovative activities that will empower young people to: contribute to and enhance health and humanities research and public engagement practices; investigate clinical and diagnostic protocols and transform clinical dialogue; shape public debate through high-quality creative outputs (exhibition/performance) that promise to be intellectually, artistically and emotionally powerful and stimulating. The co-production model at the heart of the programme will feed systematically and continually into ongoing research activities, enabling the project to stand as a beacon of good practice in engaged research and public engagement.

Amount: £147,315
Funder: The Wellcome Trust
Recipient: University of Exeter

Hydrogel-forming microneedles for periodontal bio-sensing 31 May 2018

This project aims to demonstrate that a swellable-hydrogel system of tiny projections, arranged on a thin baseplate can be used to imbibe periodontal crevicular fluid as a method of minimally invasive fluid collection. We aim to select and optimise the most appropriate microneedle design and formulation for fluid sampling from the gingival sulcus. This will involve formulation of aqueous blends of biocompatible polymers, cross-linked to form a hydrogel matrix that is hard in the dry state. This devices could be inserted between the teeth and gum margins, into the gingival sulcus where the hydrogel can swell and uptake periodontal crevicular fluid. Removing the device intact, it can be placed into an elution buffer. Pro-inflammatory biomarkers such as IL 1, IL 2 or IL 6 that have adhered to the hydrogel surface, or imbibed into the matrix can be washed off and assayed using commercially available ELISA kits. To achieve these aims, hydrogel swelling capacity and mechanical strength will be assessed using swelling studies and texture analysis for fracture force characterisation. Thin films of formulations will be cast, dried, cross-linked and assessed for cross-link density using FTIR. Commercially available ELISAs will be used to detect pro-inflammatory markers from pre-defined calibrator fluids.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Macromolecular Mechanisms of Microsporidia Infection Investigated by Cryo Electron Tomography 21 May 2018

Microsporidia are eukaryotic, intracellular parasites that infect most animals, including humans. They cause debilitating disease in immunocompromised individuals and are partly responsible for the global decline in honeybee populations. To infect a host cell, microsporidia employ a harpoon-like apparatus called polar tube (PT) that rapidly ejects from the spore, penetrates the membrane of a target tissue cell and transports the spore content (sporoplasm) into it. I propose to investigate the so-far unknown macromolecular architecture and mechanism of the PT using state-of-the-art cryo electron tomography (cryoET). The key goal is to examine the cellular machinery that facilitates PT release, sporoplasm transfer and target membrane penetration. This research will provide 3D molecular maps of the PT in action and thus detailed and dynamic understanding of the microsporidian infection pathway. The research will enrich our knowledge of fundamental cell biology, establish microsporidia as a eukaryotic model system for cryoET, inform new medical approaches to treat microsporidiosis and help fight the decline in honeybee populations. Seed Award funding will pave the way for my career as new independent group leader in the UK, with a high impact biomedical profile and will offer a plethora of opportunities to collaborate with academia and industry downstream.

Amount: £98,680
Funder: The Wellcome Trust
Recipient: University of Exeter

3D printable antimicrobial materials for the development of safer medical devices 31 May 2018

Nosocomial infections primarily result from bacterial attachment to surfaces and biofilm formation, for example of implanted medical devices. Such infections demonstrate significant resistance to antibacterial treatment, resulting in extended hospital stays, increased healthcare costs, patient morbidity and potential mortality. The incorporation of antibiotics into the surface of a medical device could prevent bacterial colonization but it contributes to the antibiotic resistance problem. A good approach to prevent this is to prepare medical devices with inherent antimicrobial properties. In the present work, we propose development of 3D printable materials containing an antimicrobial biomolecule obtained from renewable sources, lignin. For this purpose, lignin will be combined with two different 3D printable materials: poly(lactic acid) (PLA), to create solid coatings, and poly(vinyl alcohol) (PVA), to create hydrogel coatings. The present project combines the versatility of 3D printing for the preparation of medical materials with the antimicrobial properties of lignin with the aim of creating safer, greener and cheaper medical materials. The main goals of the project are: Preparation of PLA-lignin and PVA-lignin hybrid materials for 3D printing Characterization of the resulting 3D printed materials Evaluation of the antimicrobial properties of the resulting 3D printed materials

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Small molecule inhibitors of the anti-apoptotic FLIP-FADD protein-protein interaction for the treatment of non-small cell lung cancer 01 Oct 2017

In most organs and tissues, old cells are constantly dying and being replaced by new cells. This balance is critical for normal organ/tissue function and is maintained by a balance between new cells being created by cell division and old cells dying by a process known as "apoptosis". One of the key characteristics of cancers is that the old cells do not die efficiently by apoptosis and therefore accumulate giving rise to a tumour that ultimately disrupts organ function. This block in apoptosis is also a major problem when it comes to treating cancers as the effectiveness of chemotherapies and radiotherapies usually rely on their ability to activate this type of cell death. Dr Daniel Longley's team at Queen's University of Belfast have identified an intra-cellular protein called "FLIP" that plays a critical role in preventing the death of cancer cells treated with chemotherapy and radiotherapy. This protein plays a prominent role in increasing the resistance to therapy in a number of types of cancer, including non-small cell lung cancer, which is a particularly drug-resistant cancer and is the focus of this proposal. The project team plan to generate drugs to block FLIP's function and thereby overcome drug resistance and improve the therapeutic management of patients with this disease.

Amount: £1,571,668
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

The development of insulin resistance and anabolic resistance during muscle disuse: what is the role of fuel integration? 08 Nov 2017

Skeletal muscle atrophy, which occurs during short-term disuse, is thought to be due to the development of anabolic resistance of protein metabolism and insulin resistance of glucose metabolism, although their cause is currently unknown. The primary research aim of this fellowship is to establish the role of muscle fuel availability and integration in disuse-induced insulin and anabolic resistance. In collaboration with the Medical School, I will perform two randomized, placebo-controlled studies in which young, healthy participants undergo 2 days of forearm immobilisation with placebo, Acipimox (to decrease plasma lipid availability), Formoterol (to stimulate glycolytic flux), or dietary branched-chain amino acid (BCAA) manipulation, to alter substrate availability. I will combine the arteriovenous-venous forearm balance technique, that I have recently established in Exeter, with stable isotope amino acid infusion and repeated forearm muscle biopsies to quantify muscle glucose, fatty acid, and BCAA balance, oxidation, and intermediary metabolism (including muscle protein synthesis), both fasted and during a hyperinsulinaemic-euglycaemic-hyperaminoacidaemic clamp. Two periods of research at the University of Texas Medical Branch will enable me to develop skills in mass spectrometry tracer analyses and develop a network of collaborators in the USA, both crucial for my future career investigating disuse-induced muscle atrophy.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Exeter

Neurobiological mechanisms of emotional relief in adolescents with a history of sexual abuse 06 Dec 2017

Adolescents who experienced childhood sexual abuse (CSA) engage in non-suicidal self-injury (NSSI) more frequently than peers exposed to other forms of abuse or no abuse. NSSI serves an important function of relief from acute negative affect. Despite providing temporary relief from distress, NSSI is also linked to higher rates of suicide and hospitalisations and the effectiveness of current clinical interventions is limited. This may be attributed to a lack of understanding the neurobiological and behavioural mechanisms that underlie NSSI as a relief function in particular in youth who experienced CSA. To address this gap, the study aims (1) to model brain activity during distress and emotional relief (i.e., NSSI) in adolescents with and without a history of CSA using functional magnetic resonance imaging and (2) to examine if adolescents with CSA select actions to 'escape' an aversive context more quickly and often compared to non-abused peers. The ultimate goal of this translational research is to understand the neurobiological and behavioural mechanisms that confer vulnerability to NSSI following CSA (Stage 1) in order to develop effective intervention and prevention strategies to keep vulnerable teenagers safe (Stage 2) . Keywords: sexual abuse, non-suicidal self-harm, relief, functional magnetic resonance imaging, translational research

Amount: £230,048
Funder: The Wellcome Trust
Recipient: University of Exeter

Open Access Awards 2017/18 30 Sep 2018

Not available

Amount: £58,344
Funder: The Wellcome Trust
Recipient: University of Exeter

Open Access Award 2017/18 30 Sep 2018

Not available

Amount: £25,061
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Oxytocin delivery using a microarray patch for postpartum haemorrhage 31 May 2018

This project involves development of a novel microarray patch (MAP) device for the delivery of oxytocin to prevent and treat post-partum haemorrhage (PPH). Oxytocin is recommended by the World Health Organisation as the gold-standard treatment for PPH but is often not available in low income countries as it requires cold storage and a trained health professional to administer the injection. Polymeric MAPs are minimally invasive devices, consisting of an array of micro projections, up to 600 µm in length. On application they painlessly penetrate the outermost layer of the skin, the stratum corneum and imbibe interstitial skin fluid. This causes the matrix to swell and creates a continuous network through which oxytocin would reach the systemic circulation. Oxytocin would be formulated in to a drug reservoir that is separate from the MAP, such as a lyophilised tablet, which could increase its stability. Several key parameters need to be tested: 1. Ability to load adequate oxytocin levels in to a drug reservoir. 2. Ability of an adequate concentration of oxytocin to permeate the skin with a MAP and the time taken to reach therapeutic levels. 3. Stability of oxytocin in the drug reservoir at 40oC and 75% relative humidity.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

The filamentous phage assembly system as a therapeutic tool 04 Dec 2017

Antibiotic resistance is a growing healthcare concern worldwide. The rise in the number of resistant bacteria is not being matched with an increase in new antibiotics or treatments. Novel ideas harnessing modern technology therefore need to be applied to address this problem in a timely manner. In this work, a phage encoded assembly system will be assessed for its potential application as a "switch" to control bacterial proliferation. By genetic manipulation of cells and viruses, protein expression, purification and high-end electron microscopy, the structure of a virus-encoded machinery in its host bacterial cell membrane will be determined in different conformational states. Furthermore, pilot experiments will be carried out to express and purify individual protein components for downstream mechanistic and high-resolution structural studies. The knowledge gained will provide many further avenues for research on our quest to develop advanced bactericides and synthetic cell-based treatments, and will deepen our understanding of bacterial pathogenicity in crops and animals, including humans. Funding for this proposal will also open up a multitude of downstream opportunities for collaboration with academia and industry, and importantly will provide me with the means to launch the crucial next stage of my career as an independent investigator.

Amount: £99,386
Funder: The Wellcome Trust
Recipient: University of Exeter

Sustained release of drug-loaded nanoparticles from a novel vaginal ring design 31 May 2018

Sustained-release drug products are useful in prolonging the action of a drug in the body by maintaining therapeutic concentrations of the drug over extended time periods. Here, we are particularly interested in polymeric vaginal rings for long-acting vaginal administration of drugs (1). Various steroid-releasing vaginal ring products are currently marketed for hormonal contraception and estrogen replacement therapy, and a new ring device – developed in part by the Queen's University Belfast (QUB) and offering sustained release of the antiretroviral drug dapivirine for HIV prevention – is due to reach market soon. However, a major limitation of current vaginal ring technologies is that they are generally not useful for administration of either large molecule drugs or drug-loaded nanoparticles, due to limited solubility and/or diffusion in the polymeric materials used to manufacture rings. Here, we propose for the first time to test a novel vaginal ring developed at QUB for sustained release of drug-loaded nanoparticles, with potential applications in prevention/treatment of sexually transmitted infections, mucosal immunisation, and treatment of cervicovaginal cancers. The ring device comprises orifices in the ring surface which expose the underlying drug-loaded core. The ring is easy to manufacture using highly-scalable and conventional injection molding technologies.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Microneedle delivery of the anti-psychotic medicine haloperidol decanoate 31 May 2018

This project involves development of a novel dissolving microneedle array device, incorporating a nano suspension of haloperidol decanoate to provide transdermal delivery of a formulation that will dissolve in skin and act as a depot. Dissolving microneedle arrays are minimally invasive devices, consisting of an array of micro projections arranged on a baseplate in a defined configuration. These microneedles, up to 600 µm in length, are hard in the dry state and when applied to the skin using manual thumb pressure, painlessly penetrate the outermost layer of the skin, the stratum corneum. The needle tips dissolve in interstitial fluid releasing the nano suspension formulation into the viable skin tissue. Haloperidol can then be slowly and constantly be release over long periods of time to maintain constant plasma levels. A number of key parameters need to be assessed: 1. Nanosuspension formulation using a nano precipitate/ultra sonification method 2. Nanosuspension physicochemical characterisation for particle size and zeta potential 3. Formulation of microneedle arrays using aqueous blends of biocompatible polymers 4. In skin dissolution of the microneedle formulations

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

A Healthy Interest: diets, exercise, and ideal bodies in England and Holland, 1650-1800. 08 May 2018

My thesis will analyse diet and exercise advice and practices to investigate attitudes to ‘healthy bodies’ in Dutch and English printed medical literature, physician’s casebooks, patient-physician correspondence, and recipe books between 1650 and 1800. With modern concerns around increasing obesity rates and an ever-growing body of dietary advice in both medical and popular literature, a study of diets and exercise in the past can help us understand where our current ideas and ideals concerning body and health originate. The key goals of this project are to locate the health values and practices that were being promoted at this time; to assess to what extent dietary advice and ideals reached lay society; to analyse to what extent patients followed advice and made dietary and exercise considerations part of their ‘lifestyle’; and to examine attitudes to ‘healthy’ or ‘unhealthy’ bodies and bodily ideals in late seventeenth and eighteenth-century Dutch and English society. Examining manuscript and printed sources in a geographically comparative study will provide a rich and in-depth understanding of contemporary ‘health cultures’ and bodily ideals. In so doing the thesis will analyse how far we can identify the development of a modern ‘health culture’ in this period.

Amount: £99,441
Funder: The Wellcome Trust
Recipient: University of Exeter

Care, the great human tradition: A multi-disciplinary collaborative exploration of family care across time and culture 27 Jun 2018

There are 7 million family carers in the UK and their unpaid work has been valued at more than £132 billion per year. The demand for family care, however, is rapidly exceeding supply and carers experience serious physical and mental health problems as a result of their role. Novel approaches to supporting family carers are urgently required to ensure the sustainability of family care into the future. Archaeological, anthropological, and historical accounts of care may help carers to contextualise their role, enhancing wellbeing through connection with positive accounts of care across time and cultures. The aims of this project are to (1) bring scholars from archaeology, anthropology, and history together with contemporary care researchers, carers, and partner organisations, to develop the Collaboration for Applied Archaeological, Anthropological, and Historical Research and Engagement (CARE) Network and, (2) undertake scoping research for a large Collaborative Award application. The Collaborative Award will be used to develop a comprehensive account of family care across time and cultures, and create an evidence-based intervention for contemporary carers that can be delivered by a range of arts, education, and outreach organisations.

Amount: £29,050
Funder: The Wellcome Trust
Recipient: University of Exeter