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Recipients:
University College London

Results

Neural mechanisms of learning, planning, and decision-making 31 Mar 2020

This proposal examines the neural mechanisms supporting decision-making and prospective planning. We will examine how prefrontal cortex (PFC), hippocampus, and entorhinal cortex (EC) interact to support these processes. We will examine how non-human primates (NHPs) make choices in large decision spaces, particularly when novel choice-values have to be inferred ‘online’. We will test different models of value-coding, particularly whether PFC uses a ‘place-like’ and ‘grid-like’ code to construct cognitive maps of values spaces. We will examine how NHPs make ‘online’ choices when sequentially navigating between stimuli/states as rewards move or paths blocked. We will test whether ‘replay’ provides a neural mechanism supporting model-based planning. We will use Transcranial Ultrasound Stimulation to selectively disrupt regions of PFC/hippocampus/EC to examine its effect on neural selectivity and behaviour. These tasks are high-dimensional, yet amenable to mathematical description, and will be combined with high-density recordings to map these computations. Exp.3 will integrate our home-cage training system with wireless data-logging to record neural data continuously, across tasks and sleep, to examine how neural signatures change across days with learning, and acquisition of ‘learning set’. This provides the technology to continuously map the NHP brain during performance of diverse and naturalistic tasks, radically transforming primate neuroscience.

Amount: £2,580,251
Funder: The Wellcome Trust
Recipient: University College London

Mechanisms of reading development in deaf children 31 Mar 2020

Many severely and profoundly deaf children struggle to learn to read because written text is a visual representation of spoken language, to which they have limited access. I have shown that speechreading (lipreading) relates to deaf children’s reading development. Fully understanding the mechanisms underlying the speechreading-reading relationship is fundamental to harnessing speechreading as a tool to improve deaf children’s reading. My goal is to investigate this mechanism in 1) a longitudinal study, to determine the relationships between speechreading, phonological skills, language skills and reading over time and 2) in neuroimaging studies with deaf children and adults to investigate neural representations of visual speech and written text and the relationships between them. All deaf participants involved in the studies above will use speechreading. A subset will also have learned British Sign Language from an early age. Good quality early sign language exposure is beneficial to reading development in profoundly deaf children. However, the mechanism underlying this relationship is unclear. I will employ parallel methods to those used in the speechreading studies to examine 1) the longitudinal relationships between sign language, fingerspelling and reading and 2) the neural representation of these visual language inputs in deaf children and adults.

Amount: £1,580,335
Funder: The Wellcome Trust
Recipient: University College London

Circuit mechanisms that command and pattern behavioural sequences 31 Mar 2020

Animals accomplish goal-directed behaviours by performing sequences of motor actions. A central goal of neuroscience is to understand how neural circuits regulate behaviour in accordance with external events and internal drives and precisely choreograph diverse actions for a successful outcome. To meet this challenge, I will exploit the unique accessibility of the larval zebrafish and focus on a conserved behaviour – hunting – in which a sequence of discrete, specialised actions mediates pursuit and capture of prey. I will use a powerful experimental strategy that combines cellular-resolution calcium imaging, behavioural analyses, optogenetic circuit manipulations, neuroanatomical tracing and computational modelling to discover how brain-wide circuits operate at the cellular level to flexibly control the expression and coordination of behaviour. This paradigm will enable me to discover (1) how sensory and internal state information are integrated to control the sensorimotor decision to hunt, (2) how specific hunting actions are generated and (3) how command signals operate alongside dynamic sensory inputs to assemble a goal-directed sequential behaviour. Overall, the project will produce a mechanistic, cellular-resolution circuit model that explains how the brain controls and patterns multi-component behaviour. I expect this will reveal fundamental principles about the operational logic of the nervous system.

Amount: £2,078,748
Funder: The Wellcome Trust
Recipient: University College London

How cell migration and differentiation are coordinated during morphogenesis 31 Mar 2020

During development the embryo needs to generate functional organs composed of many different cell types, often originated in different embryonic location. Thus, it is clear that cell differentiation and migration need to be tightly coordinated, although they are often studied as independent processes. Here I will test the hypothesis that cell migration and differentiations are coordinated by tissue mechanics in vivo. Specifically, I will challenge the current view that cell migration is the result of differentiation, by testing instead whether the reverse occurs, i.e. migration controls differentiation. I will use neural crest cell, a multipotent embryonic cell population in which cell differentiation is always linked to cell migration. One of the problems to study biomechanics in vivo is the limited number of tools to measure and modify mechanical properties in vivo. Here I will develop new tools to analyse and change tissue stiffness in vivo. We will analyse how these mechanical changes influence cell migration and differentiation, and we will identify the molecular response elicited in the neural crest cells. We expect that this multidisciplinary project will provide answers to a central yet unresolved question in developmental biology: how cell fate and migration are integrated during embryo development.

Amount: £1,734,742
Funder: The Wellcome Trust
Recipient: University College London

Biomedical Vacation Scholarship Programme - University College London 30 Sep 2019

<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (&pound;1500 outside of London and up to &pound;2000 in London).??? It includes &pound;500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs.&nbsp; Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research.&nbsp;<br> Over 5 years of the Programme we encourage organisations to aim for:&nbsp;&nbsp;<br> <br> -At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation.&nbsp;&nbsp;<br> <br> -At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities.&nbsp;&nbsp;</p>

Amount: £197,340
Funder: The Wellcome Trust
Recipient: University College London

talking funny - sounding different 30 Sep 2019

<p>In Talking Funny, Sounding Different we will create a performance lab within the HUB, to experiment with, innovate and empower humans and their &lsquo;funny&rsquo; voices, from the written word to live theatre, from beat boxing to comedy. We will study the performance of the human voice as a potential source of anxiety and difficulty, and as a route to confidence and social contact. We will work with people with clinical voice issues, scientists, clinicians and artists to explore new art, new therapies and apply cutting edge neuroscience to our understanding of the voice and its effect on the audience. For this discretionary award, we are asking for funding for:</p> <p>meetings between the main collaborators, patient groups, &nbsp;and relevant artists and&nbsp;performers</p> <p>live events and rehearsal time to plan and develop the live events: these events will explore the possibilities of vocal performances across different groups of people, with an emphasis on people who 'sound funny' with an emphasis on voices that are rarely heard.</p>

Amount: £10,000
Funder: The Wellcome Trust
Recipient: University College London

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

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

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

One for All, All for One? 12 Sep 2019

<p style="margin-left: 0cm; margin-right: 0cm">How people think about vaccines is a global concern<u><sup>1</sup></u>. <em>&lsquo;One for All?&rsquo;</em> asks: &ldquo;How does engagement with herd immunity influence attitudes to immunisation?&rdquo;. By working in close partnership with communities, researchers, artists, healthcare professionals, experts by experience, policy-makers and creative engagement practitioners in Africa and the UK, we will co-create a range of graphic-based, online and print resources focused on herd immunity. Developing, testing, evaluating and sharing <em>&lsquo;One for All?&rsquo;</em> resources will</p> <ul> <li>Empower people who make decisions about immunisation (e.g. parents, guardians, community leaders, influencers, older children) to: <ul style="list-style-type: circle"> <li>Make informed choices about vaccination, informed by a set of resources based on robust research, common concerns and in context;</li> <li>Contribute actively and meaningfully to future research.</li> </ul> </li> <li>Enable researchers, fieldworkers, practitioners, policy-makers and healthcare professionals to &lsquo;do&rsquo; engagement with vaccines, based around concepts of herd immunity through the use of our creative, accessible and transferable resources;</li> <li>Inform research and engagement practice by testing and evaluating our central question and sharing our learning;</li> <li>Potentially reach further global audiences through strategic branding, campaigning and stakeholder engagement.</li> </ul> <p style="margin-left: 0cm; margin-right: 0cm"><em>&lsquo;One for All?&rsquo;</em> ultimately contributes to the goal of decreasing vaccine hesitancy and increasing vaccine uptake by contributing to the learning and practice of engagement with immunisation.</p>

Amount: £166,802
Funder: The Wellcome Trust
Recipient: University College London

Optical Biology 24 Jul 2019

<p>The &lsquo;Optical Biology&rsquo; PhD programme will train future research leaders to answer fundamental questions in biology by exploiting and developing state-of-the-art optical techniques. The programme brings together life scientists, physicists, chemists and computational scientists at UCL, with world-leading industrial and academic partners, to deliver an integrated training programme in the most advanced optical methods and analysis tools. This would be the first UK PhD programme offering multidisciplinary training in the major&nbsp;advanced light-based methods that are transforming all areas of biomedical research. The programme will be based at UCL, a world-leading environment where many major advances in optical techniques for biology have been developed, including ultra-fast 3D 2-photon microscopy, targeted 2-photon optogenetics, low power super-resolution imaging and whole-brain optical mapping. It will also offer students outstanding opportunities to undertake internships and training with our industrial and academic partners, promoting their career development and providing them with attractive post-PhD prospects.&nbsp;<br> <br> <em>Key programme goals:</em><br> <br> 1. To train researchers capable of developing and using state-of-the-art optical methods and associated analysis techniques.<br> <br> 2. To train researchers to use these methods to address fundamental biological problems.<br> <br> 3. To create researchers who engage, communicate and collaborate effectively with both industry and academia across disciplinary boundaries.</p>

Amount: £6,066,810
Funder: The Wellcome Trust
Recipient: University College London

UCL Wellcome 4-year PhD in Mental Health Science 24 Jul 2019

<p style="margin-left: 0cm; margin-right: 0cm">Mental illness is a major public health problem, with poorly understood causes and highly variable treatment outcomes. While mental health research training has strength within disciplines, these typically operate in parallel, greatly impeding progress in improving clinical outcomes. The <strong>UCL Wellcome 4-Year PhD in Mental Health Science</strong> is an interdisciplinary, student-centred programme, which aims to train the next generation of research and policy leaders to succeed within mental health research fields, and foster greater cross-disciplinarity in future researchers. It leverages UCL&rsquo;s outstanding mental health research environment across three broad Themes: Mechanism, Population Mental Health, and Intervention. In Year 1, students will obtain experience in these different Themes through short rotation projects and courses, including areas outside their academic background; through this they will be exposed to new concepts and techniques, learn to &ldquo;speak the language&rdquo; of the different disciplines, and spot the synergistic connections between them. For the main PhD project in Years 2-4, students will select a supervisory team and Thesis Committee across all three Themes, enabling interdisciplinary mentorship. A strong emphasis will be placed on developing a distinct and supportive cohort identity, with continual skills development and preparation for transition following the Programme, whether within or outside academia.</p>

Amount: £5,757,810
Funder: The Wellcome Trust
Recipient: University College London

Navigation to improve outcome of epilepsy surgery 30 Sep 2019

<p>Navigation to improve outcome of epilepsy surgery', Principal Investigator- Professor John<br> Duncan (UCL). The successful neurosurgical treatment of epilepsy depends on complete<br> removal of the part of the brain that gives rise to epileptic seizures, and in avoiding damage<br> to brain areas and pathways critical for functions such as vision, language, sensation and<br> motor control. Achieving these goals requires accurate 30 planning of the surgical approach<br> and resection and real time feedback during the course of surgery. This project builds upon<br> our EpiNA V platform to visualize brain structures that need to be removed to cure epilepsy,<br> and those that need to be spared, in order to avoid adverse effects. This anatomical<br> guidance will be displayed to the surgeon via a neurosurgical navigation interface so that<br> brain tissue removal is optimised, in terms of maximising the chances of remission of the<br> epilepsy and avoiding complications such a loss of part of the field of vision and of language<br> abilities.</p>

Amount: £752,983
Funder: The Wellcome Trust
Recipient: University College London

Venezuelan Refugee access to Reproductive and Sexual Health Services in Peru: Understanding and Addressing the Need 11 Jun 2019

<p style="margin-left: 0cm; margin-right: 0cm">Venezuelan-refugees are fleeing from the country&rsquo;s political and economic crisis in what has been described as an exodus projected to eclipse that of Syria&rsquo;s. To date, over half a million have arrived in Peru (second-largest intake). The Venezuelan medical-system is on the verge of collapse with an 85% pharmaceutical shortage, including vital HIV-medication and contraceptives. Those migrants arriving to recipient countries are in desperate need of the reproductive health services denied to them in Venezuela, to stem the spread of STIs and unplanned pregnancies.</p> <p style="margin-left: 0cm; margin-right: 0cm">Peru has offered a temporary-resident-permit-scheme (PTP) that ended in December 2018, inciting an influx of migrants towards the end of the year. The Peruvian medical-system (MINSA) offers free health care to those with citizenship; a bureaucratic hurdle that many Venezuelans are unable to jump for lack of appropriate documentation.</p> <p style="margin-left: 0cm; margin-right: 0cm">Working with the United Nations Population Fund (UNFPA-Peru), this project&rsquo;s key goals are to: 1)Assess the situation of Venezuelan migrants&rsquo; access to reproductive health services in Lima, 2)Ascertain services that are lacking and/or in urgent need,&nbsp;3)Make policy-recommendations and suggest necessary MINSA-worker training. Interviews, focus groups, and a survey will be undertaken. We will provide policy recommendations to the Peruvian government health-ministry&nbsp;(MINSA)&nbsp;based on the findings.</p>

Amount: £19,819
Funder: The Wellcome Trust
Recipient: University College London

Enabling imaging of cells and tissues across scales 04 Jul 2019

<p>We seek&nbsp;funding for an array tomography&nbsp;scanning electron microscope (SEM) with ATLAS 5 software together with components to upgrade an associated light microscope, to enable 3D correlative light and electron microscopy (CLEM)&nbsp;of cells and tissues with nm resolution.&nbsp;Array tomography&nbsp;SEM allows for the detection, mapping and automated imaging of serial sections of resin embedded samples and is non-destructive technology. &nbsp; This technology is transformative and&nbsp;will enable high resolution 3D correlation of molecular machineries with cellular structure and specific cell and tissue processes. Using this new technology, our initial consortium of&nbsp;PIs will address the following specific objectives:&nbsp;</p> <p style="margin-left: 0cm; margin-right: 0cm">1. &nbsp;To elucidate the mechanism of 3D patterning during organogenesis (Pichaud)</p> <p style="margin-left: 0cm; margin-right: 0cm">2. &nbsp;To characterise the fundamental principle that regulate intracellular trafficking of cargoes and membrane, storage and lysosomal degradation (Brodsky, Futter and&nbsp;Schiavo)</p> <p style="margin-left: 0cm; margin-right: 0cm">3. &nbsp;To determine&nbsp;the molecular basis for the interaction between the HIV virus and its host cells and tissues (Jolly and&nbsp;Marsh)</p> <p>4. &nbsp;To elucidate the fundamental mechanisms of nuclear remodelling during passage through mitosis (Baum)<br> <br> 5. &nbsp;To elucidate&nbsp;the connectivity underlying circuit function (Hausser and&nbsp;Wilson)</p> <p>Altogether, our proposed studies will elucidate fundamental mechanisms of cell and tissue morphogenesis, homeostasis, function repair and&nbsp;infection.</p>

Amount: £333,750
Funder: The Wellcome Trust
Recipient: University College London

High throughput automated system for next generation sequencing (NGS) library preparation 04 Jul 2019

<p style="margin-left: 0cm; margin-right: 0cm">The requested Hamilton NGS Star automated liquid handling workstation enables high-throughput automated preparation of sequencing libraries which enables basic and clinical UCL researchers to process increasing sample numbers in a consistent, reproducible and timely manner. The proposed instrument and associated auxiliary equipment includes all the necessary hardware and software and is a fully walk-away system with a capability of processing up to 96 samples per run. Special features include air displacement pipetting using CO-RE (Compressed O-Ring Expansion) technology which provides superior measurement accuracy, precision and reproducibility without aerosol generation during pick-up and ejection, reducing the possibility of cross-contamination. Each aspirate and dispense step is dynamically tracked for confidence that the indexed and multiplexed samples are processed according to the workflow. The system also includes automated barcode reading to enable sample traceability, software with file handling capabilities and on-deck thermal cycling and cooling components for custom work flows to be fully automated. It is an open system which provides flexibility to customize workflows for specific NGS applications and develop new protocols and the scope to automate downstream processes on the same platform. The equipment will directly support &pound;20M of Wellcome Trust-funded research through the generation of up to 15,000 NGS libraries.</p>

Amount: £247,322
Funder: The Wellcome Trust
Recipient: University College London

Interconnections: the MRC National Survey of Health and Development archive 16 May 2019

<p style="margin-left: 0cm; margin-right: 0cm">The main objective of the project is to sort, preserve and catalogue the administrative archive of the MRC National Survey of Health and Development (NSHD), held at UCL, to international standards and make it available to researchers.<strong> </strong>The project will be managed by the Head of Archives, UCL Special Collections, and the project archivist will be embedded in the management structure of that department. The NSHD archive will be housed with other specialist education archives at the UCL Institute of Education.</p> <p style="margin-left: 0cm; margin-right: 0cm"><strong>&nbsp;<strong>The aims of the project are:</strong></strong></p> <ul> <li>Removal, sorting and repackaging of archive material from the current storage</li> <li>Appraisal of remaining archive material to remove duplicates and to agree retention</li> <li>Repackaging of archive material into acid-free folders and boxes</li> <li>Cataloguing of the archive using CALM, in line with international standards (ISAD(G) and ISAAR(CPF)). The catalogue will be added to the archive online catalogue (<u>http://archive.ioe.ac.uk/DServe</u>)</li> <li>Conservation and digitisation of specified material in the archive</li> <li>Creation of a records management plan to streamline future retention of material</li> <li>Outreach and dissemination work relating to the archive collection in collaboration with staff at the MRC Unit for Lifelong and Ageing at UCL (LHA).</li> </ul>

Amount: £63,290
Funder: The Wellcome Trust
Recipient: University College London

Biosocial Birth Cohort Research. A cross-disciplinary network 02 May 2019

<p>This project establishes the first cross-disciplinary international network of social scientists, geneticists and epidemiologists focused on longitudinal birth cohort studies in the Global North and South. Birth cohorts are increasingly recognised as important for understanding how biological, social, and environmental processes interact over time. This makes them central to an emerging terrain of what has been described as &lsquo;biosocial&rsquo; research. Despite this, however, relatively few social scientists have engaged with or investigated longitudinal birth cohorts. There is an urgent need to co-ordinate and consolidate emerging efforts in this area to ensure that biological and social science research benefits from productive cross-disciplinary engagement.&nbsp;The proposed network &lsquo;Biosocial Birth Cohort Research&rsquo; (BBCR) will enable a community of international researchers to examine the social, ethical and methodological challenges and opportunities of developing innovative cross-disciplinary research with birth cohort studies. It will be the first network dedicated to critically examining&nbsp;<em>and&nbsp;</em>intervening on the co-production of birth cohorts and biosocial science.</p>

Amount: £29,401
Funder: The Wellcome Trust
Recipient: University College London

Studies in Hypochondria 05 May 2019

<p>&ldquo;Studies in Hypochondria&rdquo; is an interdisciplinary, medical humanities project that charts changing conceptualisations of the relationship between health and illness through a literary and cultural history of the figure who troubles our ability to make that distinction: the hypochondriac. By reading medical and historical texts, I show how in the late nineteenth and early twentieth centuries, hypochondria lost its longstanding association with melancholy and hysteria, and took on its modern meaning as an excessive fear that one is suffering from disease. At this time the hypochondriac became the object of ridicule and scorn. I historicize these cultural shifts, arguing that, in its modern form, hypochondria arose in the late Victorian period as an anxious response to increased knowledge of disease and its diverse aetiologies. I argue that hypochondriacal doubt is constructed by the very medical discourses that it calls into question. Furthermore, through a series of literary &ldquo;case studies&rdquo; I examine hypochondria&rsquo;s complex relationship with literature. By turning to three celebrated and self-described hypochondriac writers, I show how hypochondria has repeatedly been mobilized by artists and writers as a means of testing, often sceptically, the certainties of Enlightenment rationality and medicine.<br> &nbsp;</p>

Amount: £98,620
Funder: The Wellcome Trust
Recipient: University College London

Subversive Practices: Traditions of Talismanic Healing in the Making of Modern China, c. 1850–1949 05 May 2019

<p style="margin-left: 0cm; margin-right: 0cm">Throughout Chinese history, talismans have been central to healing for the vast majority of the population. From the Sui to the Qing dynasties (581-1644), talismans formed an imperially-sponsored medical discipline, after which they were permanently forsaken by the court. However, despite subsequent condemnation by the state, talismans remained pervasive throughout Chinese society until the first half of the twentieth century. This can be attested by the publication of an unprecedented wave of cheap almanacs and manuals of talismanic healing, as well as a dynamic economy revolving around these practices between the 1850s and 1940s. Paradoxically, this was precisely the period when the Chinese state began to marginalize talismans and other healing rituals from China&rsquo;s public sphere, condemning them as at odds with a &quot;modern&quot; Chinese medicine.&nbsp;Combining historical and ethnographic analysis, I will examine the marginalization and survival of talismanic culture in Republican China (1912&ndash;1949). Print culture will provide copious textual evidence of the circulation of talismanic knowledge in Shanghai and the place of talismanic healers in its healthcare market, while fieldwork with a talismanic healer will offer a case study that ties together the historical and anthropological strands in an analysis of contemporary transmission and practice of talismanic healing.</p>

Amount: £141,717
Funder: The Wellcome Trust
Recipient: University College London

RNA metabolism in developing neurons 16 Jul 2019

<p>Understanding how neurons translate extracellular cues into specific patterns of gene expression is amongst the major goals of modern neurobiology. Efforts to unravel the molecular basis of localised gene expression have mostly focused on transcriptional control and mRNA transport. However, post-transcriptional mRNA processing is increasingly recognised as an essential step in the propagation of genetic information. Importantly, incorrect processing and delivery of mRNA causes developmental defects and severe human neurological disorders. The overarching scope of this project is to investigate novel mechanisms of mRNA metabolism that are likely to be conserved in all mammalian cells and to provide new insights regarding how gene expression is regulated in neurons.&nbsp;The 3&rsquo; untranslated regions (3&rsquo;UTRs) of RNA transcripts play a key role in mediating many steps of RNA metabolism, including splicing, nuclear export and localization. We performed 3&rsquo;end-Seq screens of transcripts localised in sub-cellular compartments of sympathetic neurons and are uniquely positioned to tackle the question of how 3&rsquo;UTRs regulate RNA metabolism in neurons.<br> We will address the following questions:</p> <ol style="list-style-type: upper-alpha"> <li><em>What determines the fate of a bifunctional&nbsp;mRNA? </em></li> <li><em>Does the 3&rsquo;UTR influence the proteome in sympathetic neurons?</em></li> <li><em>Do 3&rsquo;UTRs generate a new class of RNAs that regulate neuronal development?</em></li> </ol>

Amount: £2,119,443
Funder: The Wellcome Trust
Recipient: University College London