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Results

Timestamping Integrative Approach to Understand Secondary Envelopment of Human Cytomegalovirus 28 Nov 2017

The mechanisms facilitating the assembly of Human cytomegalovirus (HCMV) in the cytoplasm of infected cells, a complex process termed ‘secondary envelopment’, are poorly understood. Our goal is to identify in-situ the identity, position, and interactions of all the essential proteins involved in this critical stage of the viral ‘lifecycle’. Despite decades of research, it has been difficult to dissect the complexity of secondary envelopment, as bulk assays only show ensemble averages of populations of viral particles. To study these intermediates that are formed when cytoplasmic capsids acquire tegument proteins and their envelope membrane, we will develop a novel approach that separates these intermediates in time and space. We will provide their spatio-temporal models by integrating complementary cutting-edge techniques and expertise within this collaboration, including flow-virometry, correlative (fluorescence and electron cryo) microscopy, crosslinking and ion-mobility mass spectrometry-based proteomics, and computational modelling. Specifically, we aim to: -Identify key players in tegument assembly on capsids/membranes. -Elucidate the order and spatial organisation of tegument assembly. -Validate the interactions in vivo and analyse capsid tegumentation in vitro. -Integrate the information into a spatiotemporal model. This will significantly improve our understanding of herpesvirus assembly in general, a crucial step towards identifying new therapeutic targets.

Amount: £673,700
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Open Access Awards 2017/18 30 Sep 2018

Not available

Amount: £21,050
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Toddlerlab CAVE Neuroimaging Facilities 05 Jul 2018

The Centre for Brain and Cognitive Development (CBCD) has been at the forefront of developing behavioural, electrophysiological, and functional Near Infrared Spectroscopy (fNIRS) methods for use in early development. We propose to assemble the world’s first audiovisually contingent, fully immersive multiuser Cave Automatic Virtual Environment (CAVE) incorporating real-time synchronised brain recordings of electrical activity, blood oxygenation, and motor functioning (motion tracking, EMG), all using wearable or wireless technology enabling natural toddler and pre-school child interactions to be recorded. This will be achieved by building a completely new dedicated facility incorporating state of the art behavioural and neuroimaging capabilities. The proposed automated end-to-end pipeline will provide an unconstrained solution that will allow toddlers and pre-school children to be studied in comparable ways to infant and animal studies, affording direct validation of existing animal models of cognitive development to neurotypical development, as well as to emerging disorders, such as ADHD, Autism Spectrum Disorder, Down syndrome, and Williams syndrome. This facility will allow us to join the dots between early neurocognitive development, which is relatively well understood, and later development in middle childhood that will enable the direct translation of advances in basic bioscience to practical clinical and social solutions.

Amount: £850,458
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Deciphering the molecular mechanisms of autism: A computational search for differential poly-adenylation events in neurexin-deficient worms 31 May 2018

Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder, but, despite a large body of studies, its molecular basis remains largely unknown. Meta-analysis of public transcriptomic data has suggested that the mechanism of alternative poly-adenylation (APA) might be dysregulated in the autistic brain. APA determines the length of the transcripts’ tails and thus indirectly controls temporal and spatial regulation of gene expression in mammalian cells by including or excluding regulatory elements from the 3’ untranslated region. APA has been implicated in disease, most notably cancer, but its link to ASD was only recently suggested and warrants further investigation. To circumvent challenges associated with using human tissue, this project suggests testing the presence of differential poly-adenylation events in a very simple model of autism, the neurexin-deficient C. elegans. Nematode worms lacking neurexin have been suggested as simple models for the study of molecular perturbations in ASD. This project will employ bioinformatics approaches to search in-house RNA-seq data of eight samples from wild-type and neurexin-deficient worms for significantly different APA events. Results from this study could be compared to findings in the autistic brain data and could help us design experiments to better understand the origin and effects of this dysregulation.

Amount: £0
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

History of Medicine: Minds, Bodies and Cultures 11 Jul 2018

The MA in History of Medicine runs for one year full-time or two years part-time, during which students complete two core courses and three subject-specific option modules. The first core course—'Mastering Historical Research’—introduces students to the important debates and schools of thought that have shaped the discipline of history. The other core course—'Research Skills for Historians’—prepares students for dissertation-writing. Both aim to establish pathways for progression to doctoral research. The option modules represent HCA’s diverse research expertise. Unlike HSTM MAs at many other institutions, we explore health and illness from antiquity to the present day, equipping students with the conceptual knowledge and analytical skills to draw meaningful comparisons across many centuries and great cultural and geographical divides. Our MA provides students with a rich and varied experience of studying history at a postgraduate level, allowing them to satisfy and expand their passion for the history of medicine and health. But our primary focus is always to transform these passions into meaningful research—to help students build the intellectual and methodological foundations to undertake sophisticated and original projects that prepare them for doctoral work and professional life.

Amount: £87,705
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

History of Medicine: Minds, Bodies and Cultures 30 Jun 2018

Recent historical work has begun to grapple with the ways in which representations of epidemics in the Global South have impacted both popular understandings and policies towards afflicted countries. Previous studies such as David Campbell’s ‘The Iconography of Famine’ have shown how visual culture has played an important role in both presenting the Global South as inferior to the West and in prompting government actions. There is, however, a need for more scholarly attention to be focused on historical representations of Ebola epidemics and the impact that such representations have had in social and political spheres. By contextualising my close analysis of Ebola photography within a diverse selection of textual sources, this project will fulfil the following three objectives: 1. Explore the ways in which photographs of the Ebola epidemic in British popular culture have historically shaped attitudes and policies towards afflicted countries. 2. Produce a peer-reviewed article that will examine the history of photographic representations of Ebola in Britain. 3. Submit an opinion piece to Guardian Science that will explore visual imagery in relation to current debates over public-health and immigration policies. Further, a policy report will be produced for History & Policy.

Amount: £25,175
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Data Worlds and Futures: Archives, Bioinformation and Evidence 27 Jun 2018

As body fragments, tissue samples and DNA sequences are progressively transformed into highly mobile and replicable data, bioinformation raises urgent questions about the entanglement of (life and) death with the materialities and mechanisms of data worlds. This project explores the relation between bioinformation, infrastructures and evidence in relation to forensic archival practices and data processing. It examines the social lives of data through practitioners’ day-to-day activities, social practices of collection, storage and use through associations that privilege particular data types and configurations. An integrated programme of activities will: 1) establish a research network of bioinformation scholars; 2) engage forensic specialists and data scientists in two collaborative workshops to explore the digitisation and storage of biomaterials and the algorithmic applications used to interpret data and produce evidence; 3) produce exploratory empirical research at a forensic services provider and repository, as a background case study to analyse digitisation and data processing in forensic research and forensic service provision. This project will open up major areas of enquiry that will improve public understandings of evidence intersecting forensic science, genetic profiling, and algorithmic processing. It will foster new avenues in bioinformation research, data policy and algorithmic governance in the field of health and wellbeing.

Amount: £29,084
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Waiting Times 01 Feb 2017

This project brings together an interdisciplinary team to investigate waiting as a cultural and psychosocial concept, and an embodied and historical experience, in order to understand the temporalities of healthcare. It represents a fundamental rethinking of the relation between time and care through a critical analysis of waiting in the modern period. Working across Medical Humanities and Psychosocial Studies, we will uncover the history, cultural representation, and psychosocial organisation of delayed and impeded time, from 1860 to the present. This work will underpin focused investigations of ‘watchful waiting’ in current general practice, psychotherapy, and end of life care. We ask which models of time operate within healthcare practices and develop new models of durational temporality to conceptualise how waiting can operate as a form of careful attention, historically and in the present. Contextualising these healthcare practices within broader social organisations of time, we open up the meanings, potentialities, and difficulties of waiting in current times. Through academic publications and extensive public engagement, we will reframe debates about waiting in and for healthcare, moving beyond the urgent need to reduce waiting times in the NHS, towards a more comprehensive understanding of the relation between waiting, care, and changing experiences of time.

Amount: £636,821
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

State of the art cryo electron microscope for molecular and cellular biology 07 Dec 2016

Dramatic advances in the power of cryo electron microscopy (EM) to resolve macromolecular and cellular machinery have greatly expanded the field and our need for access to state-of-the-art microscopes. With its internationally renowned research programme on macromolecular machines, the ISMB EM lab is ideally placed to benefit from recent instrumental developments. Although the eBIC facility at Diamond helps by providing intermittent access to state of the art 300 kV systems, this cannot sustain our large research programmes and expanding user base without substantial in-house facilities. Our ever-increasing number of structural and cell biology users are now waiting 3-5 weeks for access to high-end microscopes. Our recent equipment award contributes to an intermediate, 200 kV system, suitable for single-particle work but sub-optimal for tomography and cell biology, limiting its wider impact. In contrast, a 300 kV machine, with cutting-edge performance for single particles, unique assemblies, and cellular sections, would have a transformative impact, enabling new research from a wider community including outstanding local cell biologists. Therefore, we request a Cryo-EM Equipment Grant to upgrade from the 200 kV system to a high-end 300 kV system to be accommodated by an expansion and reorganisation of our EM laboratory.

Amount: £2,340,000
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Sexual Violence, Medicine, and Psychiatry 01 Feb 2017

Medical professionals play central roles in examining, treating, and counselling victims of sexual violence. Their scrutiny of the complainant’s body is decisive in determining whether or not the police take the assault seriously and whether legal proceedings are instigated. Women, men, and children who are sexually abused depend on the medical and psychiatric professionals for physical and emotional care. Physicians play significant roles in determining whether an accused person is subsequently convicted, punished, or treated. The research focuses on the constituent parts of the UK, US, Australia, and New Zealand between the first decade of the nineteenth century and the present. It sets out to promote human health through providing unprecedented insights into the role of medicine and psychiatry in understanding, interpreting, treating, prosecuting, and preventing sexual violence in the context of four Research Streams: 1) Medicine and Law; 2) GPs, Police Surgeons and Forensic Medical Examiners; 3) From Psychopathia Sexualis to the DSM/ICD; 4) Psychiatric Aftermaths. There will also be a research theme on child sexual abuse, attached to one or more of the Research Streams. The project will be a powerful example of how historical scholarship can inform contemporary crises and debates.

Amount: £1,237,585
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Characterising the neutralising antibody response in chronic hepatitis C virus infection 31 Jan 2017

Despite new treatment options there remains ~180 million people chronically infected with Hepatitis C virus (HCV), and, with 3-4 million new infections every year, a preventative vaccine is the greatest unmet need in tackling the HCV pandemic. A key challenge for the development of an effective vaccine is HCV’s ability to evade and disable the human immune response. This includes an array of neutralizing antibody (nAbs) evasion mechanisms. Nonetheless, nAbs contribute to the control of chronic infection and can prevent infection in various challenge models. The aim of this project will be to characterise the natural nAb response to HCV using a novel combination of computational and experimental methods. Key goals are to: characterize the nAb responses in chronically infected and acute resolving patients, including the epitope specificity of anti-HCV nAbs; understand where key epitope residues fit into the context of HCV glycoprotein structure, with potential insights into how nAbs drive viral evolution; model the impact of mutations to better understand the structural determinants of nAb evasion. This work may directly contribute to future vaccine design.

Amount: £0
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

High resolution cryo-tomography structures of the COPII coat assembled on membranes 31 Jan 2017

Vesicle formation at the Endoplasmic Reticulum (ER) is a key seminal step in the intracellular delivery of proteins and lipids in Eukaryotes, and is governed by the highly conserved coat protein complex II (COPII). Previous cryo-electron tomography (Cryo-ET) of cell-free COPII vesicle-budding assays has revealed a membrane-proximal lattice ("inner coat") and a membrane-distal lattice ("outer coat"). Application of novel subtomogram averaging (STA) routines has elucidated the basic geometric properties of these lattices, and how COPII is deployed to sculpt a range of membrane morphologies. Using recent developments in EM data collection and processing, a new cryo-ET dataset for these assays will be obtained. Higher resolution STA reconstructions of the COPII assembly will be proposed, providing a platform to investigate the role of the inner and outer coat in vesicle formation. The elusive connections between the coats will also be interrogated to better understand the hierarchical COPII assembly. The project will require comprehensive training using the in-house electron microscopes, as well as application and optimisation of recent methodologies in STA and structural modelling. Wet-lab work will include expression and purification of yeast COPII proteins, and optimisation of the assay conditions for cryo-ET.

Amount: £0
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Structure and Action of the Metazoan Disaggregase Complex 31 Jan 2017

The metazoan Hsp70 disaggregase system is the only known human protein complex capable of resolubilising aggregated protein, conferring a protective phenotype for a range of pathologies. Disaggregation occurs through the dynamic assembly of a Hsp70/110 complex, initiated by J-protein recruitment of substrate. The structure of the active complex is currently unknown, as is the mechanism of disaggregation. This project will employ an interdisciplinary approach to structurally characterise the disaggregation of alpha-synuclein amyloid fibres in vitro by the human proteins DNAJB1 (J-protein), Hsc70 (Hsp70) and Apg2 (Hsp110). There will be a primary focus on understanding two particular elements of disaggregation. Firstly, how do J-proteins recruit substrate to activate disaggregation? This will be investigated using electron tomography, taking advantage of the recent "resolution revolution" in the electron microscopy field. Secondly, what is the mechanism of the active disaggregase complex as it is resolubilising aggregates? To answer this, we aim to track individual alpha-synuclein fibres by atomic force microscopy and total internal reflection fluorescence microscopy as they are solubilised during disaggregation. Given the role of aggregation in a broad range of debilitating diseases, increasing the understanding of disaggregation in humans has the potential to eventually lead to significant public health benefits.

Amount: £0
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Feeling Flesh: Pain, Emotion and the Self in the Understanding of Insanity’s Tortured Bodies and Fractured Minds, c.1880-1930 02 May 2017

This study draws attention to the ambiguities and conflicts surrounding embodiment and pain in late-nineteenth and early-twentieth century understanding of the experience of ‘insanity’. Engaging with concepts of embodied cognition, the history of emotion and phenomenology, it considers the relationship between the body, culture, and language in the experience and construction of disorder. Deconstructing boundaries drawn around the ‘shell-shocked body’ in historical discourse draws attention to the ambiguous but shifting position occupied by the hypersensitive uncontrollable or pained body to reveal the experience of mental illness as shaped by a complex interaction of body, language, and culture. Resistant reading of patient case-notes and published treatises on insanity will be used in conjunction with a consideration of representations of the ‘insane body’ in the visual arts (including photography and film). Arguing for a biopsychosocial approach to mental health, this research emphasises the importance of historicising the ways in which the experience of ‘disorder’ is filtered through textual and visual discourse; asking how patients have communicated sensation and considers the ways in which doctors have sought to record or understand it.

Amount: £89,933
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Fascism, the Corruption of Psychiatry and the Coercion and Confinement of LGBT People in Italy, 1922 - 1943 02 May 2017

My doctoral thesis will draw together substancial archives records and will analyse the complex and intricate behind-the-scenes dialogue between psychiatric hospitals directors, public security forces, local authorities, mental health patients and their families during the fascist regime in Italy (1922-1943). Analysing and comparing the correspondence between these institutions and individuals, together with doctors' and nurses' notes, in four different locations, it will shed light on how repression of so-called sexual inversion was implemented. This fragmented and choral dialogue will be revealing of broader social attitudes towards homosexuality and will challenge the stereotype of cohesive Italian families that was so central in fascist propaganda. It will unravel mechanisms of power and authority during the regime and will show to what extent its rhetoric had entered everyday life. Finally, it will demonstrate how the law and its representatives accommodated the regime's need to isolate and punish non-conforming individuals, and how psychiatry offered its knowledge to this project, thus becoming its most effective tool of repression.

Amount: £96,076
Funder: The Wellcome Trust
Recipient: Birkbeck University of London
Amount: £150,535
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Hiding in Plain Sight. Cultures of Harm in Residential Institutions for Long-Term Adult Care, Britain 1945 to 1980s 24 Jan 2017

During the 1970s and early ‘80s, 18 major investigations were conducted into abuse and neglect in long-stay psychiatric hospitals. These inquiries focused primarily on administrative and management failures, giving little attention to the underlying values and belief systems – staff attitudes to pain, suffering, institutionalisation and care – that gave rise to abusive practices, or to the language and behaviours that perpetuated them. In this project, I will return to the extensive documentation generated by two of these inquiries, together with other sources, and ask new and different questions to gain deeper insights into the underlying factors that gave rise to institutional abuse in order to help prevent it in the future. Through a number of publications (one monograph and at least two research-based journal articles) as well as workshops the project will provide current inquiries, policy-makers, health workers and clinicians, and social scientists with valuable historical context around abuse, whilst introducing a new strand of inquiry into historical scholarship. Engagement with the wider public is vital for a project such as this and I will regularly contribute opinion pieces for the wider media (newspapers, blogs, public talks, radio), and write at least one theatre or radio play.

Amount: £229,852
Funder: The Wellcome Trust
Recipient: Birkbeck University of London

Establishing objective measures for identifying children with Autism Spectrum Disorders using eye-tracking technology in the UK and India 09 Nov 2016

Autism Spectrum Disorders (ASD) contribute significantly to total years lived with disability globally. Most people with ASD in low-income countries are belatedly or never diagnosed, mainly due to the paucity of mental health specialists - hence critical years for treatment are missed. Objective measures for ASD detection are needed. Multiple cognitive markers of ASD have been identified using eye-tracking technology; testing these markers in combination holds promise for effective identification of children with ASD. This proposal aims to establish objective measures for identifying children with ASD using eye-tracking technology in high and low-income settings. Stage 1 will analyse existing eye-tracking data from the British Autism Study of Infant Siblings, to establish a combination of eye-tracking tasks that has the highest probability of identifying children with an ASD diagnosis. Stage 2 will be a case control pilot study to determine whether the same combination of markers identifies children with an ASD diagnosis in India. The feasibility and acceptability of these eye-tracking tasks will also be assessed in an Indian context. Establishing effective, acceptable and feasible methods for objectively identifying children with ASD will improve detection in these settings and translate into a greater number of children benefiting from early interventions worldwide.

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

Institutional Strategic Support Fund 07 Sep 2016

Not available

Amount: £900,000
Funder: The Wellcome Trust
Recipient: Birkbeck University of London