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Results

Expanding the capabilities and use of the South West Regional Facility for High-Resolution Electron Cryo-microscopy 07 Dec 2016

State-of-the-art direct electron detectors (DEDs) and new image processing strategies enable electron cryo-microscopy (cryoEM) routinely to achieve near-atomic resolution of biological samples. CryoEM has thus become a primary imaging technique, increasing the need for research institutions to provide cutting-edge cryoEM equipment. The Living Systems Institute (LSI) at the University of Exeter is a brand new interdisciplinary research centre, which will develop strategies to study diseases and their prevention. As part of the GW4 group (also including Bristol, Bath and Cardiff), we seek to develop regional research infrastructure on a scale beyond the capabilities of the single institutions. Within this remit, the Wellcome Trust-funded South West Regional Facility for High-Resolution Electron Cryo-microscopy will be established in Bristol, with a 200kV cutting-edge cryo electron microscope at its core. To support this venture and significantly increase the capabilities of the facility for all users within GW4, we plan to contribute a state-of-the art K3 DED with energy-filter. We also plan to establish an entry-level multiuser cryoEM facility at the LSI, supporting the research needs of local users in order to provide samples for further high-resolution analysis in Bristol and at the Wellcome Trust-funded electron Bio-Imaging Centre (eBIC) at Diamond.

Amount: £1,000,000
Funder: The Wellcome Trust
Recipient: University of Exeter

The role of protein tyrosine phosphatase 1B ( PTP1B ) in generation of tolergenic dendritic cells 31 May 2018

In homeostatic conditions dendritic cells are tolerogenic (Tol DC) and therefore, supress immune reactions, making them a key element in the maintenance of peripheral tolerance. Upon challenge, these Tol DC convert into mature, pro-inflammatory DC capable of initiating immune responses, this conversion is key in the induction of uveitis. It has been demonstrated that Tol DCs exhibit hyperphosphorylation of STAT3, a component of JAK/STAT signalling pathway, which is critical in controlling DC function. Previously, the lab has demonstrated that protein tyrosine phosphatase 1B is a key regulator of DC function via a STAT3 dependent mechanism. This project will investigate the role of PTP1B in intrinsic STAT3 regulation in DC by utilising a novel DC specific PTP1B knock out model (Zbtb46-PTP1B). I hypothesis that deletion of PTP1B in DC will result in hyperphosphorylation of STAT3, and preservation of Tol DC phenotype upon inflammatory challenge. Firstly, maturation status will be assessed through surface and intracellular flow cytometry for key DC activation markers (CD40, CD68, CD40, MHC class II) and cytokines (IL-12 and IL-10). Secondly, through assessment of key signalling pathways (JAK-STAT, PI3K-AKT, ERK1/2) involved in DC function, through western blotting, to allow mechanistic insight into the signalling pathways controlling Tol DC phenotype.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Aberdeen

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

Santorio Santorio and the Emergence of Quantifying Procedures in Medicine at the End of the Renaissance: Problems, Context, Ideas. 12 Jan 2015

While mechanics and astronomy have always been placed at the heart of the major narrative of the scientific revolution, historians are currently reconsidering disciplines or ways of thinking once regarded as peripheral, in particular medical disciplines such as anatomy and physiology. In this context, a study on the Italian physician Santorio Santorio (1561-1636) could be particularly noteworthy. Santorio is reputed to be the first to conceive and apply the quantification of the so called 'persp iratio insensibilis' in his major work 'Ars de statica medicina' (Venice 1614). Although developed in the context of traditional medicine, concepts such as 'weight', 'measurement' and 'certainty' became essential pillars of his thought and for this reason, Santorio invented many scientific devices, among which were the first graded thermometers. Despite his relevance, however, there are no recent studies on Santorio. The goal of my research would be to illustrate the medical impetus towards cont rolled experimentation and quantitative measurement in the cultural context of the end of the Renaissance. Considering Santorio's wide legacy across the Europe, the research would also show how the development of instruments has driven medicine in the late seventeenth and early eighteenth centuries.

Amount: £127,884
Funder: The Wellcome Trust
Recipient: University of Exeter

Gender stereotypes in ADHD diagnosis. 31 Mar 2015

This small-scale social epidemiology project seeks to establish evidence for a gender bias in the diagnosis of childhood Attention Deficit Hyperactivity Disorder (ADHD). It will question whether boys are more likely to receive a diagnosis than girls, given equally severe symptoms. Social epidemiologists in child psychiatry have suggested there is likely to be both real differences in ADHD symptomology between genders and additional referral / identification bias towards boys. The latter m ay be because ADHD is stereotyped as a 'male disorder', therefore boys are more likely to be assigned the label, whereas girls with comparable difficulties are overlooked. The methodology will be a secondary analysis of data from a birth cohort which comprises 14,000 children. Two groups, one with, and one without ADHD diagnosis will be matched on symptom severity. Gender ratios will be compared between these two groups. It is important to establish whether there is referral/ labelling bia s to help clinicians recognise girls who might benefit from ADHD diagnosis. The findings will also inform on-going debates about over-diagnosis of ADHD in boys. Outputs include one journal article, a press release, and workshops with ADHD charities.

Amount: £4,985
Funder: The Wellcome Trust
Recipient: University of Exeter

Detinova on Safari: Forgotten Histories of Global Health. 27 Oct 2014

This pilot project explores the influences of Soviet tropical medicine in Sub-Saharan Africa. It takes as its focus a method of mosquito dissection pioneered in the 1940s by a team of vector biologists based at the Moscow Martsinovsky Institute. The Detinova Technique offered a way to determine the exact physiological age of the female mosquito and provided insight into the dynamics of disease transmission. Heralded as a game-changer for global malaria eradication efforts, the technique prompted new collaborations and rivalries between East and West. The global health trajectory of this method reveals alternative histories of malaria control through a rather different set of techno-scientific circulations than those commonly associated with the WHO. Extending previous ethnographic and archival research conducted in Africa with archival and memory work in Russia and the UK, this project explores the significance of this scientific exchange for our current understandings of malaria contr ol and the Cold War, advancing a rapprochement in Anglo-Russian histories of global health.

Amount: £4,977
Funder: The Wellcome Trust
Recipient: University of Exeter

Biomedical Vacation Scholarship 22 Jun 2015

Not available

Amount: £7,500
Funder: The Wellcome Trust
Recipient: University of Aberdeen

MA History 30 Jul 2017

My project researches associations between fat bodies and gender in the medical literature of early modern Europe. While modern concerns with increasing rates of obesity are reflected by a growing historical scholarship on this topic, much remains to be examined, especially concerning the link between cultural ideas about fat bodies and the medical understandings of these bodies. The purpose of this research is to assess gendered ideas in early modern medical discussions on obesity. I will do so by examining European medical texts between 1650 and 1750, particularly comparing English medical debates with those occurring in the Netherlands in the same period. The goal of this comparison is to locate and explain differences in the extent to which gendered assumptions about obesity informed medical debates in each country, in different schools of thought, and even between individuals. I will assess the nature and causes of different explanations and treatments of obesity within the context of cultural, as well as medical developments, unique to period, place, and practitioner. I will demonstrate how and why gender played a role in the diagnosis and prescriptions for cures of obesity.

Amount: £22,440
Funder: The Wellcome Trust
Recipient: University of Exeter
Amount: £63,702
Funder: The Wellcome Trust
Recipient: University of Exeter

In vitro characterisation of neurons and glia derived from mouse ES cells having Y chromosome gene deficiencies 27 Apr 2017

The brain is a sexually dimorphic organ, which can explain why many psychiatric disorders are gender-biased. While it has been thought that fetal sex hormones play a crutial role in brain sexual differentiation, emerging evidence indicates that genetic and/or epigenetic factors encoded by sex chromosome genes are also involved. Here, we focus on several Y-linked genes expressed in the male brain, which may act in a dominant manner. Sry, Uty and Smcy genes, whose products can participate in histone modification, are of particular interest. However, their functions in the brain remain unknown mainly because of difficulties in conventional gene-targeting of Y loci in embryonic stem cells (ESCs). In this project, we will take advantage of Crispr/Cas genome-editing technology that allows us to modify Y-linked genes. Mutant alleles of these three genes in ESCs were created and then differentiation will be induced of neurons and glia from the mutant ES cells. Differential gene expression between wild-type and mutant cells will be analysed by RT-RCR and bisulfite PCR, and subsequently epigenetic status of these differential genes will be elucidated. The project will reveal influences of Y-linked genes on sex-specific epigenetic modification and lead to better understanding of gender-biased psychiatric disorders.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Aberdeen

University of Exeter Medical Humanities Postgraduate Conference. 27 May 2014

The Centre for Medical History at the University of Exeter will be holding a two day interdisciplinary medical humanities conference for postgraduate students on the 24th and 25th July 2014. The conference will bring together the highest quality postgraduate research in all fields of the medical humanities and encourage cross-disciplinary discussion. In addition to papers from forty delegates the event will also include two keynote addresses, a panel discussion with keynotes and department membe rs, and a presentation from Wellcome Trust representatives about humanities funding opportunities.

Amount: £1,000
Funder: The Wellcome Trust
Recipient: University of Exeter

Two-day international, multidisciplinary workshop on migration and health - particularly mental health - in historical and contemporary contexts, to be held at the University of Aberdeen, April 2014. 18 Nov 2013

The application is for support towards the costs of a two-day workshop, to be held at the University of Aberdeen from 10-11 April 2014. The primary theme of the workshop is Migration and Mental Health and it will explore in greater depth issues that were raised at a panel session on migration which was held during the annual Association for Medical Humanities conference in Aberdeen in July 2013. It will also build, more specifically, on a two-day symposium to be held in Halifax, Nova Scotia, in November 2013. The Canadian event, which is being co-organised by the applicant under the auspices of Saint Mary's University, Halifax, and the Gorsebrook Research Institute for Atlantic Canada Studies, is entitled Medicine and Migration: historical & contemporary dimensions. Canadian speakers will be joined by the applicant and another speaker from the UK. Aberdeen University is at the forefront of Medical Humanities in Scotland and the workshop will strengthen that profile. The applicant is e ngaged in collaborative interdisciplinary work with colleagues in Aberdeen, elsewhere in Scotland, the UK, and overseas. The workshop, which is expected to attract approximately 25 participants, will enhance and expand these networks and highlight a marginalised area of study.

Amount: £4,880
Funder: The Wellcome Trust
Recipient: University of Aberdeen

Yesterday's Doctors: Multidisciplinarity in British Medical Education since 1945. 18 Jan 2013

Overall the research will involve 2.5 weeks of archival research on multidisciplinary medical education in Britain since 1945, focusing on the integration of ethics, philosophy, history, social science and the arts into undergraduate curricula and intercalated Masters degrees. These 2.5 weeks will be used as follows: - 2 days: Wellcome Library archives (including medical ethics education 1964-93 and General Medical Council records). - 6 days: Papers of three London medical school archives. - 2 days: Royal College of General Practitioners archives (education). - 1 day: National Archives (medical education). - 5/6 days: two university special collections (Manchester/Aberdeen) as case studies for comparative purposes with London. This research will be used alongside printed primary materials to inform three activities: a) the presentation of papers on Anglo-American medical education since 1945 at the iCHSTM 2013 in Manchester and at EAHMH 2013 in Lisbon (abstracts currently under consideration); b) the publication of an original article for BMJ's Medical Humanities and a shorter commentary for Medical Education; c) development of a proposal for a larger postdoctoral research project which will examine the twentieth-century humanisation of Anglo-American healthcare and medical education.

Amount: £2,051
Funder: The Wellcome Trust
Recipient: University of Exeter

The Medical World of Early Modern England, Wales and Ireland, c. 1500-1715. 31 Jan 2012

This project will develop and make public a groundbreaking database with biographies of all medical practitioners active in England, Wales and Ireland c.1500-1715, which will then be used to produce the first all-round study of the nature and impact of medical practice in early modern Britain, to be published as a major monograph by a leading university press. The database will build on a prototype already created by Dr Peter Elmer, a senior researcher on the project (which already includes much of the necessary coverage for England, and some material for Wales and Ireland), to which will be added information from existing databases of other scholars, notably Dr Margaret Pelling, and from family and local history groups. Research assistants with expertise in Welsh and Irish sources/languages will be employed to ensure full coverage of those countries. The database (hosted initially by the Centre for Medical History (CMH) at Exeter) will be developed as a permanent online resource, link ed to other existing online resources, with the facility for others to add to the database under controlled arrangements. The project researchers, together with other CMH staff (directed by Professor Barry), will analyse the data on medical practitioners to produce the first comprehensive analysis of early modern British medical practitioners. This will explore not only their education, career patterns and medical activities, but also their major contribution to science, the arts, business, reli gious and political thought, revealing the key contribution of medical practitioners to the revolutionary changes in Britains place in the world.

Amount: £923,122
Funder: The Wellcome Trust
Recipient: University of Exeter

New insights from neonatal diabetes 15 May 2012

Not available

Amount: £1,456,000
Funder: The Wellcome Trust
Recipient: University of Exeter

Mode of delivery after caesarean section: An investigation of offspring risks and factors influencing women's attitudes towards delivery options. 21 Jun 2012

This project aims to address major issues associated with our ever increasing caesarean section (C/S) rate. Offspring risks of elective repeat caesarean section (ERCS) will be studied, including medical conditions potentially associated with a lack of exposure to labour and delivery. Factors which affect attitudes towards mode of delivery in a first pregnancy and following a C/S will be investigated, along with the effect of these factors on intended and eventual delivery mode. We plan to conduc t a retrospective cohort study comparing incidence of various medical conditions in offspring delivered by ERCS with those aiming for vaginal birth after C/S (VBAC) in Scotland. We will systematically review existing literature on factors affecting preferences for ERCS or VBAC. We will use these findings to inform a questionnaire study of psychological factors affecting preferred mode of delivery using a Theory of Planned Behaviour approach in; Group 1) women in their first pregnancy, who will r eceive the same questionnaire during mid-pregnancy and in the post-natal period, consisting of closed-ended questions; Group 2) Women in their second pregnancy after a previous C/S, who will receive an extended version of the questionnaire received by group 1, including open-ended questions.

Amount: £220,774
Funder: The Wellcome Trust
Recipient: University of Aberdeen

The Cross-Disciplinary Invention of Sexuality: Sexual Science Beyond the Medical, 1890-1940. 20 Jan 2015

This project represents a fundamental rethinking of the emergence of the scientific study of human sexuality in the c19th and reconsiders how modern understandings of sexuality were constructed. We critique the hitherto dominant assumption that 'sexology' existed as a clearly understood and primarily medical field of knowledge. We present a new account of the rise of a cross-disciplinary 'sexual science' driven by dissatisfaction with exclusively medical approaches. From the 1890s, medical docto rs argued that a properly scientific understanding of sexuality required input from additional areas of knowledge (e.g. anthropology, sociology, history, literature). This project offers the first full investigation of the conceptual and cultural factors driving the evolution of a cross-disciplinary sexual science: the desire to understand the global variety of sexual behaviour; an interest in historical and cultural variation; and a new focus on the 'normal' and 'healthy' alongside the 'path ological' and 'abnormal'. We examine the ways in which these studies challenged biological explanations of sexuality, raising questions about the 'nature/nurture' divide, and brought imperially-shaped debates about race, the primitive, civilization and degeneration into the heart of sexual science. Thus the project sheds new light on the evolution of a range of categories that are central to understandings of human behaviour in the modern world. Interdisciplinary collaborations will produce m onographs, journal issues and edited collections. A stakeholder-led engagement programme will raise broader questions about the relation between medical and non-medical forms of knowledge in the past and present to address contemporary challenges surrounding sexual health and wellbeing.

Amount: £425,352
Funder: The Wellcome Trust
Recipient: University of Exeter

Lifestyle, health and disease: changing concepts of balancein modern medicine. 29 May 2015

In 2008, Dr Margaret Chan, Director-General of the WHO, suggested that: `A world that is out of balance in matters of health is neither stable nor secure.' By explaining global health in terms of balance, Dr Chan was mobilising traditional medical beliefs in the relationship between physiological, psychological and political stability and health, from ancient humoral medicine through to modern injunctions to maintain physical balance and fitness, achieve work-life balance, and protect the bala nce of nature in order to safeguard health and well-being. The aim of this research is to analyse ways in which changing notions of balance have shaped scientific and clinical models of healthy lifestyles and to understand the manner in which preoccupations with balance have structured our lives. The central premise is that balance has constituted not only an object for scientific and clinical enquiry, but also a rhetorical construct employed to articulate shifting anxieties about well-bei ng, environmental sustainability, and political security. Research will focus on three overlapping themes: 1. The development, application and reception of scientific theories of, and therapeutic strategies for attaining, bodily balance. 2. Scientific and clinical accounts and patient experiences of coping with mental illness and maintaining work-life balance. 3. Arguments about the relationship between ecological balance and the prevention of chronic diseases, including mental illness, obesity and heart disease. Academic publications, impact activities and the creation of a critical mass of inter-disciplinary researchers will generate a richer understanding of clinical approaches to, and experiences of, changing relationships between lifestyle, health and disease.

Amount: £100,000
Funder: The Wellcome Trust
Recipient: University of Exeter

Open access award 2011/12. 20 Sep 2011

Not available

Amount: £30,000
Funder: The Wellcome Trust
Recipient: University of Exeter