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Recipients:
University College London
University of Cambridge
Award Year:
2018

Results

Health, Medicine and Society 11 Jul 2018

The MPhil in Health, Medicine and Society (HMS) provides students with interdisciplinary training in the history, philosophy, anthropology and sociology of health and medicine. The programme is structured around taught modules across the four disciplines. These are keyed to three research essays (one pass/fail of 3,000 words; two of 5,000 words), supported by one-to-one supervisions. Students are guided by an overall course manager and individual subject managers to choose their modules and to identify a dissertation topic. The 15,000-word dissertation, also supported by one-to-one supervision, allows students to master a particular topic and the appropriate methods for addressing it. The programme is distinctive in training students in these four disciplines. No other programme in the UK does this. Moreover, because it is situated within a vibrant international hub of humanities and social sciences research in health and medicine, students are supervised by leading scholars in the field. Students arrive with a first-class degree (or equivalent) and learn to think critically and independently, employing a range of methods, about the meanings of health and medicine. HMS was launched in 2017, and from the outset has attracted outstanding students with tremendous promise for the future.

Amount: £94,994
Funder: The Wellcome Trust
Recipient: University of Cambridge

Menstruation and the moon in early modern England 08 May 2018

The association of menstrual synchrony with the moon relates back to ancient mythologies. Historians largely dismiss the relevance of a lunar theory of menstruation by the Middle Ages, but the moon’s ability to disturb a woman’s womb through her menstrual blood was continuously discussed by early modern medical and natural philosophical writers. This project asks how the sympathetic connection between menstruation and the moon was manifest in learned discourses, vernacular knowledge, and everyday practices. Answering this requires studying women’s knowledge, the relationship between natural and occult philosophy, and the link between theory and practice in medicine. This research draws together rich, diverse manuscript and printed sources to demonstrate how the influence of the moon over the female body was ubiquitous in early modern medicine and natural philosophy. In vernacular medical handbooks, the moon was a popular socio-cultural symbol of femininity and sexual difference. Its power over the female body was demonstrated through practice in recipe books, casebooks, female-authored almanacs and medical treatises on phlebotomy. The cause and consequences of its influence were debated through learned discourse, highlighting the temporal dynamics of menstruation, and the continuous significance of fluids to changing intellectual frameworks of the body.

Amount: £100,057
Funder: The Wellcome Trust
Recipient: University of Cambridge

The Future of Maternity Care: challenges and opportunities to achieve person-centred care in the NHS 18 Jun 2018

I propose to review up-to-date research and evidence regarding new developments in technology and health education that aim to improve maternity care in the UK, particularly through improving women’s access to information, services, and their own medical records. Parliamentarians will require a balanced and concise summary of the evidence behind these new technologies and a sense of how they will be received by the public and health professionals. Key goals: Assess the work that has come out of the National Maternity Review, particularly advances in e-health and mobile technology such as the Digital Maternity Toolset being developed by NHS Digital Look more generally at the opportunities for health education in maternal health Explore the possibility of learning from policy innovations in other health systems Engage with a range of stakeholders over the course of the project to assess how policy recommendations will be received and identify potential areas for improvement

Amount: £6,514
Funder: The Wellcome Trust
Recipient: University College London

Residues and remains: Anthropology of practices around pregnancy endings 23 Jul 2018

My research explores the practices around pregnancy endings and their remains, including acts of forgetting and remembering, and asks what do these reveal about the status of foetuses, women and mothers in contemporary England? Pregnancy endings provide opportunities to interrogate anthropological assumptions about the contemporary family, motherhood, personhood and kinship. To analyse this, I will focus on the practices in the aftermath of a pregnancy ending to understand what they reveal about the values afforded to the remains in different contexts (clinic, home, burial site, crematorium, grave site etc) and by different stakeholders. My research will explore how reactions to and practices around pregnancy endings and remains reflect wider cultural trends in the UK, particularly around motherhood as highly moralized and notions of foetal personhood. I ask how does grief (or the absence of it) intersect with the relationship of the materiality of the remains and the woman’s body. I will conduct in-depth, embedded and analytic ethnography at the Rose Hill Clinic, East Oxford and other sites. Key outputs include a monograph, 3-4 journal articles, and materials aimed at women/ couples (i.e. newspaper articles, information video, radio/ television), health professionals and relevant others (i.e funeral providers, support groups).

Amount: £388,698
Funder: The Wellcome Trust
Recipient: University College London

A Hotbed for Liver Cancer: Biomedicine, Exposure and Uncertainty in West Africa 23 Jan 2018

Incidence rates of primary liver cancer vary strikingly across the globe. West Africans are more likely than most populations to develop and die from it. Focusing on Senegal and The Gambia, my project investigates how this association between place and intensity of susceptibility to liver cancer has been understood, and how it has been maintained by gaps in protection from risky exposures and fatal illness. Its key goals are to: 1) Situate biomedical models of liver cancer aetiology and prevention in West Africa, by tracing the emergence of current biomedical knowledge and uncovering past and alternative explanations. 2) Delineate the past and emerging contours of partial, public prevention of exposure to major risks factors: chronic infection with Hepatitis B Virus and food contaminated by aflatoxin (toxic metabolites of fungi that colonize crops, notably groundnuts). 3) Observe the embodiment, materialization and enactment of liver cancer in local moral economies and infrastructures of care, and identify the dilemmas that arise. Combining historical and ethnographic methods, this project aims to elucidate how endemic exposures and intrinsic limits of care have been mutually shaped, in West Africa, by contingent political, economic and scientific histories of partial protection.

Amount: £301,612
Funder: The Wellcome Trust
Recipient: University College London

Changing In/Fertilities 30 Jan 2018

In contrast to the promotion of planned parenthood which dominated the early and mid 20th century, it is the spectre of unplanned infertility that has beome more prominent in the early 21st century.Changing In/Fertilities is designed to facilitate the urgent task of more explicitly characterising post-ART fertility transitions through a global collaborative project uniting 24 research projects in 16 different countries. Over a three year period this large team will explore changing perceptions of fertility, fertility imaginaries, fertility fears and fertility behaviours in the post-ART context. We will document in ‘thick’ qualitative detail the often surprising and unexpected ways in which fertility is being re-imagined and redefined, and also how new fertility trajectories intersect – for example in the effort simultaneously to encourage women to begin their reproductive lives earlier, whilst offering increasing options to extend fertility. We will identify key factors and drivers linking the expansion of ARTs to fertility change, and these will feed into policy as well as basic scinece. Our detailed studies of situted fertility transitions will support a sustained comparative exercise that will in turn yield a more general sociological theory of post-ART fertility change.

Amount: £1,419,802
Funder: The Wellcome Trust
Recipient: University of Cambridge

Technologies of Health c. 1450-1750 23 Jan 2018

This project investigates the production, use and impact of everyday health technologies in Britain and the global world c. 1450-1750. It explores a wide range of objects from Issac Newton's drawing of an ear trumpet to birthing chairs to patient records. Using a series of detailed case studies, it seeks to understand how technologies crucially influenced past sickness experiences, medical encounters and healthcare provisions and contemporary attitudes towards materials, skills and tools. The focus on the quotidian and, particularly, on how users adopted and modified technologies, will offer a view of medicine from the ground up, highlighting the dynamic relationship between patient and practitioner, user and maker and expert and lay. In doing so, it will revise existing narratives of early modern medical practice, answering calls to foster closer connections between histories of science, medicine and technology. Recognising the importance of colonial and commercial forces, it will also interrogate the relationship between expanding empires and ‘local’ ideas about health and the body. It will produce two main outputs - a monograph titled 'Technologies of Health in Early Modern Britain' and an edited volume of essays accompanied by a project website with a blog and a virtual exhibition of 'object studies'.

Amount: £258,969
Funder: The Wellcome Trust
Recipient: University College London

Youth, gender and teenage sexual counselling in Britain: The making of the Brook Advisory Centre, 1964-2000 23 Jan 2018

This research uses the history of Brook Advisory Centres (BAC) as a case study through which to reassess the history of teenage sexuality and of the anxieties it caused in postwar Britain. From the first Centre opened in 1964 in London to the present, BAC has been an important provider of contraceptive advice and sexual counselling for unmarried people and teenagers. Although the centres have provoked fierce opposition and triggered recurrent public debates on teenage sexuality, little is known of their history. As a non-governmental organisation which however had clear connections with the Family Planning Association and the National Health Service, BAC provides an insightful locus to explore the way teenage sexuality was handled and debated publicly. Using the newly catalogued archives of BAC together with other sources, this research is divided in three parts. Part I examines the relationship between sexual culture and sexual politics by exploring the conditions under which teenagers and unmarried people became target for contraceptive advice. Part II looks at the content of sexual counselling and the extent to which clients’ demands and experiences shaped them. Part III explores the cultural dimension of reproductive politics by uncovering the impact of mass media on BAC’s orientation.

Amount: £155,453
Funder: The Wellcome Trust
Recipient: University of Cambridge

Politics, medical knowledge and development: from Israel to Ethiopia and Eritrea (and back) 07 Mar 2018

This project will critically study how the circulation of medical knowledge and practices of developing health programs between Israel, Ethiopia and Eritrea, shape regional politics, immigration dynamics and racialization processes in Africa and the Middle East. Specifically, how political instrumentalisation of medical knowledge affects three interrelated dynamics: Constructing health development schemes that facilitated an Israeli strategic foothold in Ethiopia. Establishing a strainer mechanism to sift through the Ethiopian Jews immigrating to Israel and legitimising the detention and potential incarceration of Eritrean asylum seekers upon their arrival to Israel's border with Egypt. The project's principal goals are: 1. Conducting exploratory research into the medical interactions between Israel, Ethiopia, and Eritrea. 2. Developing a research platform including an advisory board, research workshop, a panel in an international conference, and a digital archive. 3. Consolidating an academic network for an intellectual community of leading scholars and early career researchers examining the politics of medical development in the Middle East and Africa. 4. Constructing a platform and network as the first phase of research exploring the political legacies of medical development and health aid in the Global South.

Amount: £29,330
Funder: The Wellcome Trust
Recipient: University College London

Understanding Medical Black Boxes: A Philosophical Analysis of AI Explainability 26 Jul 2018

I plan during the next two years to develop a major, multi-year project into AI explainability in medical contexts. This project will connect existing literatures in philosophy of science, philosophy of medicine and medical ethics, where problems of understanding and explanation have been extensively studied, to the emerging literature on explainability in machine learning and the ethics of AI. The aim will be (i) to enhance our understanding of the problems AI systems raise for explainability in medical contexts and (ii) to collaborate with machine learning researchers to develop technical research apt to address these problems. The existing literatures on explainability and understanding in medicine are vast and have not previously been systematically connected to the ethics of AI. To lay the groundworks for a later grant proposal, this application proposes to conduct three pilot-studies, focusing on potential challenges from AI to: (1) mechanistic understanding, (2) clinical judgement and diagnostic reasoning and (3) informed consent. A part-time research assistant will assist in scoping the relevant literatures. Travel to groups at other universities and a workshop in Cambridge will furthermore help establish contacts with a network of researchers interested in the ethics of AI and AI explainability in medical contexts.

Amount: £86,561
Funder: The Wellcome Trust
Recipient: University of Cambridge

Infectious science engagement activities in post-Ebola Sierra Leone 30 Jan 2018

Having experienced the Ebola epidemic first-hand, we realised that the majority of the population did not know what a pathogen was, creating fear and misbeliefs that hampered outbreak control. There is a clear need for science engagement and an opportunity to provide it now. We have found school children to be highly tuned into discussions about Ebola and other pathogens. Now is the right time to broaden their awareness of infectious diseases beyond Ebola, and to engage their curiosity through science creating a positive legacy. We aim to: - Engage young people in Sierra Leone in the science of infectious diseases that are all around them, sparking their scientific curiosity and making conversations about pathogens commonplace. - Empower young people with the understanding that if they know how infectious diseases spread, they can prevent infections, improving their health and that of those around them. - Excite young people about science and encourage scientific studies and careers.

Amount: £144,350
Funder: The Wellcome Trust
Recipient: University of Cambridge

Politics, Philosophy and Economics of Health 30 Jun 2018

This project will examine benefits sharing for the provision of genetic information in the creation of medical treatments for infectious diseases. Networks to enable the international sharing of genetic material are a cornerstone of pandemic preparedness initiatives. Countries with the highest disease burdens share their isolated virus strains, that are utilised by pharmaceutical companies to create patented therapies, typically inaccessible to the citizens of the country from which they originated. The inequity of such a system is clear. In response to Indonesia’s 2006 protest, the Pandemic Influenza Preparedness Framework (PIP) was developed to facilitate benefits sharing. Uniquely, this framework set a standard of practice for governments, academics, and the private sector, and enabled it to be enforced through the use of civil contractual legislation. However, recent scientific and technological advancements, such as gene sequencing data (GSD), may serve to diminish the framework’s capacity to promote global health justice. Through an evaluation of the effectiveness and equity of current policy, this research attempts to highlight areas of tensions that arise in light of recent innovation. If left unaddressed, these new gaps could impede the goal of fairness that these policies set out to achieve, directly impacting the health of individuals globally.

Amount: £27,140
Funder: The Wellcome Trust
Recipient: University College London

Does ROCK-dependant actomyosin activity kick-start nuclear descent during inter-kinetic nuclear migration in the mammalian neuroepithelium? 31 May 2018

In the posterior neuropore (PNP), actomyosin-driven apical constriction reduces the apical surface area of neuroepithelial cells, aiding neural fold apposition. This constriction is superimposed on changes in apical dimensions due to interkinetic nuclear migration (IKNM). Regional IKNM regulation is believed to alter PNP architecture, but the degree to which IKNM is linked to force generating apical constriction is unknown. The host lab recently showed that inhibiting the actomyosin-regulating Rho-associated protein kinase (ROCK) produces an atypical bimodal distribution of apical dimensions. This, alongside heterogeneous phospho-myosin light chain (pMLC)II staining, suggests only a subset of neuroepithelial cells are actively constricting at any one time. We hypothesise: ROCK-dependent active apical constriction at the end of mitosis initiates neuroepithelial nuclear descent in IKNM. To address this, I will use CD1 mouse embryos to: Compare apical dimensions and pMLCII immunofluorescent staining of neuroepithelial cells in M phase, G1, and intervening phases by confocal microscopy. Establish the time course of apical area changes and pMLCII staining following ROCK inhibitor treatment. Determine if apical area changes induced by ROCK inhibition is cell cycle phase dependent. Produce descriptive 3D in silico models of nuclear movements and apical dimensions for neuroepithelial cells with/without ROCK inhibition from confocal images.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

Investigating notch signalling in patient-derived models of familial Alzheimer's Disease. 31 May 2018

Alzheimer's Disease (AD) is characterised pathologically by extracellular plaques composed of Abeta peptides, which are generated by the successive proteolytic processing of the amyloid precursor protein (APP) by multiple enzymes including the gamma-secretase complex. Human genetics supports a causative role for Abeta in AD: mutations and gene duplications in APP cause familial AD. Further, mutations in PSEN, which forms part of the gamma-secretase complex, are also causative of fAD. However, substantial clinical heterogeneity exists in fAD patients with PSEN1 mutations, the molecular basis of which is not well understood. Our hypothesis is that differential processing of non-APP substrates of gamma secretase may contribute to neurodegeneration in fAD. The aim of this project is to investigate the processing of non-APP substrates of gamma-secretase in fAD, using induced pluripotent stem cell-derived neurons from 7 fAD patients with mutations in APP and PSEN1 and age/sex matched controls. Specifically, we will use western blot to analyse the notch pathway in fAD and control lines and understand if this pathway is dysregulated in AD. This project will allow us to determine if the processing of non-APP substrates of gamma secretase is altered in fAD patient cell models, forming the basis for further mechanistic studies.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

Developing statistical learning methods to infer how higher-order genomic architecture influences phenotypes 30 Sep 2018

Since the completion of the Human Genome Project, big genomic data is becoming available at an unprecedented scale. The early genome-wide association studies (GWAS) that followed, which sought to relate phenotypic differences to genomic variation, revealed that many diseases have complex aetiologies, where a combination of genetic and environmental factors contribute to the development of traits, with their relative importance quantified by heritability. Simultaneously, in recent years, neural-networks emerged as a powerful framework to solve non-linear prediction tasks, but hitherto have not been applied to the GWAS problem yet. During my first year, I developed an artificial deep neural-network prototype, which utilised heritability to obtain a higher phenotype prediction accuracy, compared to baseline models. In my full PhD project, I will build on my early successes. First, I will make my framework more applicable to larger and smaller datasets. Then I will move onto creating tools that may provide insight into the aetiology of traits and finally, I plan to expand my methods to incorporate multi-omic data into the model. I hope that my research project will contribute to the development of tailored therapies that may provide a more effective approach to prevent or treat complex diseases in the future.

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

Evaluating the Co-Inheritance of Alpha-Thalassemia and Sickle Cell Anaemia and its Impact on Haematological Indices 31 May 2018

Sickle Cell Anaemia (SCA), the most severe and most common form of sickle cell disease, is a major public health problem in sub-Saharan Africa. Homozygosity for sickle haemoglobin (HbSS) causes SCA but the clinical phenotype is variable in severity. Alpha-thalassemia, caused by deletions in the alpha-globin genes, co-exists at very high frequencies in the same sub-Saharan African regions as the sickle cell trait (HbAS). Nigeria has the highest burden of SCA globally but there is limited information on the co-inheritance of SCA and alpha-thalassemia in Nigerians and reports from other sub-Saharan African countries have given differing results. Ethnic diversity in Nigeria necessitates ascertainment of information from different geographic regions. While personalised medicine is not realistic in sub-Saharan Africa at present, it is important to obtain information on variation, relevant for healthcare provision at the community level. This study aims to investigate the relationship between the alpha-globin gene deletions (3.7kb and 4.2kb) and haematological indices in SCA patients and controls from Abuja.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

The role of the Trem2 R47H mutation in the development of Alzheimer disease phenotypes in APP knock-in mice 31 May 2018

The field of research into Alzheimer’s disease is lacking a transgenic mouse model which shows progressive degeneration like in humans. Recently, there has been increased interest in the involvement of the immune system of the central nervous system, particularly microglia, which co-localise with amyloid-beta plaques, potentially limiting toxicity. TREM2 is a protein expressed by microglia and the R47H mutation is an identified risk-factor for Alzheimer’s disease. We propose that combining this microglial risk-factor with raising amyloid beta in APP knock-in mice may exacerbate the Alzheimer's phenotype, potentially leading to tau pathology. Initially I will be taught to perform whole-cell voltage-clamp in brain slices. I will then use a novel TREM2(R47H) knock-in mouse and examine variables previously reported as altered in transgenic APP/PSEN1 mice (and confirmed in APP knock-in mice, unpublished). In particular I will record spontaneous and miniature excitatory postsynaptic currents, the frequency of which is dependent on the probability of glutamate release and number of synapses; the amplitude dependant on the number of postsynaptic receptors. These experiments will help to elucidate the effects of microglia in early synaptic changes involved in AD and will provide initial characterisation of the TREM2 mice that will be crossed with APP knock-in mice.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

Local cAMP regulation of the slow after-hyperpolarization 31 May 2018

The slow afterhyperpolarization (sAHP) occurs following trains of action potentials, and it plays a crucial role in regulating neuronal excitability. It determines the timing of action potential firing, thereby modulating neuronal processes including synaptic plasticity. The sAHP has important implications for disease, since elevated neuronal activity is associated with neurological disorders including epilepsy. Currently, little is know of how the sAHP is regulated at the molecular level. The aim of this research project is to investigate at the molecular level how the second messenger cyclic AMP suppresses the sAHP. This summer project will use a combination of molecular biology and electrophysiology to investigate sAHPs in hippocampal CA1 pyramidal neurons in rat brain slices. Two specific aims will be pursued. First, an anchoring disruptor peptide will be applied to determine whether anchoring of cAMP-dependent protein kinase (PKA) is required for sAHP suppression. Second, we will utilise novel tools for manipulating the phosphorylation state of PKA regulatory subunits to investigate the hypothesis that PKA regulatory subunit phosphorylation supports sAHP suppression by PKA. This approach has the potential to reveal important molecular features of an important physiological process with implications for neurological disorders.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London

Inhibitory Mechanisms Of Homeostatic Plasticity In Vivo 17 Jul 2018

Homeostatic plasticity is the compensatory mechanisms that regulate activity levels in the brain during ongoing changes, for example following learning or input loss. To date, homeostatic plasticity studies have largely focused on changes in excitatory neurons; however, inhibitory neurons also play an important role in regulating overall network activity. Given the known connectivity of excitatory and inhibitory neurons in mouse visual cortex, changing activity in different inhibitory subtypes would have drastically different effects on network activity, but the role of specific inhibitory subtypes in homeostatic plasticity is unclear. We will use in vivo two-photon imaging in behaving adult mice expressing genetically encoded calcium indicators to measure the activity levels of inhibitory subtypes during the homeostatic recovery of activity that follows the loss of sensory input to the visual cortex. We will then use optogenetic tools to change activity levels in these inhibitory subtypes, to determine: 1) their causal role in the maintenance of activity after homeostatic activity recovery, and 2) their interactions with homeostatic plasticity mechanisms that facilitate homeostatic recovery. These experiments will identify which inhibitory subtypes are critical for homeostatic plasticity.

Amount: £1,566,641
Funder: The Wellcome Trust
Recipient: University College London

NMR structural studies of protein folding during biosynthesis on the ribosome 30 Sep 2018

Proteins must fold into their tertiary structure in order to function. This complex process has been well studied over recent decades. However, most of these studies rely on small isolated proteins; protein folding inside of cells can be very different. In cells during translation, the ribosome synthesises proteins by adding amino acids to the growing polypeptide chain, this eventually extends out of the ribosome tunnel and can can begin to fold while still being synthesised; representing a major difference between historical folding studies and the real picture inside cells. In our lab we aim to characterise the process of protein folding on the ribosome. We are especially interested in how the ribosome may aid proteins to fold efficiently. To do this we use Nuclear Magnetic Resonance (NMR) spectroscopy to generate structural information of proteins attached to ribosomes alongside Cryo Electron Microscopy and Molecular dynamics computer simulations. This PhD project will aim to fully characterise the structure and dynamics of a nascent chain attached to the ribosome using a variety of NMR experiments. We will then analyse a variety of proteins to try and understand why they fold at different points during translation.

Amount: £0
Funder: The Wellcome Trust
Recipient: University College London