NIHRDataInsights/HRCSData huggingface dataset:
Title: Viral and cellular regulation of T-cell amino acid metabolism
Funder: Medical Research Council

Abstract: I previously used TMT-based plasma membrane proteomics to gain a comprehensive, unbiased overview of cell surface proteins regulated by HIV infection, and discovered HIV-mediated downregulation of >100 novel plasma membrane protein targets. Amongst these, the amino acid transporter SNAT1 was downregulated by the HIV accessory protein Vpu, and the putative serine carriers SERINC3/5 were downregulated by Nef. I identified alanine as an endogenous SNAT1 substrate, and showed that uptake of alanine is essential for T-cell mitogenesis. I also saw Nef- and Vpu-independent regulation of numerous other transmembrane transporters, suggesting a general paradigm for HIV-mediated manipulation of nutrient uptake and cellular metabolism. I now wish to (1) characterise the roles of alanine and SERINC3/5 in T-cell amino acid metabolism; (2) discover new metabolic pathways targeted by HIV in T-cells; and (3) identify key amino acid transporters and metabolic pathways required for T-cell mitogenesis. Along with alanine transport by SNAT1, ER-resident SERINC proteins incorporate serine into membrane phospholipids. In the 1st part of my project, I will therefore use radiolabelled amino acid transport and stable isotope-labelled metabolite tracing techniques to elucidate the role of alanine in T-cell metabolism, and determine whether cell surface SERINC3/5 act as T-cell amino acid incorporators or transporters. In the 2nd part of my project, I will use Antibody-Free Magnetic Cell Sorting (AFMACS) to isolate HIV-infected T-cells, apply a comprehensive, unbiased metabolomic approach to identify dysregulated metabolic pathways, and determine the mechanisms and viral genes responsible. Finally, in the 3rd part of my project, I will develop a combined plasma membrane proteomic and CRISPR-based genetic screening strategy to determine which transmembrane transporters and metabolic pathways are required for T-cell mitogenesis, focussing on mechanisms for glutamine and net amino acid uptake.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Characterization of the human extra-embryonic macrophage population, Hofbauer cells, phenotype and function
Funder: Wellcome Trust

Abstract: Macrophages are among the first immune cells to seed embryonic tissues. They play important roles in early fetal development including tissue modeling and maintaining healthy tissue homeostasis. In humans, macrophages are present in the villous core of the placenta before a vascular connection with the embryo and these extra-embryonic macrophages, termed Hofbauer cells (HBC) are readily available for study. Developing our understanding of HBC and the role they play throughout gestation is important as they lie at the interface between the mother and fetus. HBC are likely to regulate placenta development, in particular the trophoblast cells that are the ultimate barrier between mother and fetus. HBC are also an important fetal defense against transplacental infections and in utero fetal infections are associated with pathogens that can survive in macrophages. However, the functions of HBC are poorly understood. Through this proposal, using some of the most advanced tools available today including multi-parameter flow cytometry, mass cytometry, RNA sequencing and organoid cultures, I will provide the first in-depth characterization of the human placenta extra-embryonic macrophages, HBC. I aim to describe the phenotype of HBC, their transcriptomic profile and functional properties. Keywords: Human extra-embryonic macrophages, Hofbauer cells, placenta, vertical-transmission, fetus, immunity.

Lay abstract: The human placenta is a major signaling organ that regulates the health of both the mother and developing fetus during pregnancy. The placenta is generally thought to consist of two sides the maternal and the fetal side. While we have some understanding of the biology of maternal-derived immune cells within the placenta, our understanding of fetal-derived immune cells is still extremely poor. In particular, I am interested in studying fetal-derived macrophages within the placenta, commonly termed Hofbauer cells (HBC). HBC are thought to play a key role in placenta development and in defending the developing fetus from infection. However, we still have little understanding of how HBC do this. This is particularly relevant for pathogens such as Zika virus which seem to be able to cross the placenta from the mother to infect the fetus. Through this study I hope to develop better techniques to identify HBC, highlight the importance of HBC in placenta development and demonstrate how HBC help protect the fetus from infection.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: RECOVERY/Phase 2 Therapeutic Trials Reconfiguration
Funder: Medical Research Council

Abstract: The RECOVERY trial is jointly funded by the NIHR and UK Research and Innovation (UKRI), with research delivery supported by the NIHR’s Clinical Research Network at 176 hospital sites across the UK. The trial is being coordinated by researchers at the University of Oxford, which acts as the sponsor for the research. This award is jointly funded (50:50) between the UKRI and the NIHR. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. With this support, to date the trial has recruited over 12,000 participants - making it the world's largest trial of potential COVID-19 treatments RECOVERY/Phase 2 Therapeutic Trials Reconfiguration also known as Recovery+ is additional support to continue the work of the initial RECOVERY trial titled COVID-19: multi-arm, multi stage adaptive clinical trial (CoV-MAMS) – MC_PC_19056


Research activity codes: 6.1 PHARMACEUTICALS;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM;RESPIRATORY
Title: Role of the oral microbiome & mucosal immunity in COVID-19 disease: diagnostic/prognostic utility in South Asian populations
Funder: Medical Research Council

Abstract: SARS-CoV2 (CoV2) primarily infects respiratory mucosae, yet the role of mucosal immunity is not known. UK South Asian (SA) patients have a higher mortality from CoV2 infection than most ethnic groups, whereas in India similarly adjusted mortality rates are lower than in the UK. We hypothesise that mucosal immunity plays a role in susceptibility to and severity of COVID-19 and explains these differences. Minor salivary glands appear to be major sites of CoV2 replication leading to extremely high viral counts in saliva and upregulated production of cytokines. Mucosal surfaces have their own microbiome which protects against pathogens and oral, lung & nasal microbiomes are closely related. Microbiome dysbiosis may be a factor in COVID-19 severity. This study will therefore compare the oral microbiome, salivary innate and specific mucosal antibody responses longitudinally among CoV2-positive SA patients in India and the UK and determine their diagnostic and prognostic utility. Healthy controls and CoV2-positive patients of SA origin with asymptomatic or symptomatic disease or who are COVID recovered will be recruited in the UK and India. Blood and stimulated whole mouth saliva (SWMF) samples will be collected longitudinally for up to 90 days from infected individuals. Cytokines, T cell phenotypes and IgA & IgG anti-CoV2 antibodies will be determined in SWMF and compared with those in blood. The SWMF microbiome will be analysed by shotgun metagenomics and the metabolome by using NMR. The influence of pre-existing mouth disease in susceptibility to COVID will be determined. Identification of these factors should result in direct and applicable clinical benefit to SA populations and others. Ongoing collaborations between London and Chennai will facilitate commencement of these studies. In London, samples will be taken from patients who are also part of a partner proposal (KCL-SIMS), enabling saving on research costs.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM;RESPIRATORY
Title: Pilot of an Intervention for Malawian Pregnant Women with HIV to Improve Depression, Viral Suppression and Engagement of Partners in HIV Self-Testing
Funder: Medical Research Council

Abstract: The aim of the proposed study is to pilot a combination of evidence-based interventions aimed at Malawian pregnant women living with HIV, and their male partners. The long-term goal is to move towards joint management of mental health and strengthening of the HIV care cascade for HIV-positive women. The study will take place in Bangwe antenatal clinic, Blantyre, which registers 145 new ANC patients per week with an HIV prevalence of 15%. Aim 1: Finalise TENDAI-Together, a task-shifted intervention originally developed and successfully piloted in Zimbabwe, to treat depression and optimise adherence to antiretroviral therapy (ART) for antenatal women living with HIV in Malawi. This will include formative work, comprising focus group discussions and in-depth interviews with 30 key informants. Key aims are to ensure the relevance of the checklist of barriers to ART adherence for the Malawian antenatal context, and to gather views and approaches about involve the woman's partner, or an alternative significant other, in two of the sessions. Aim 2: Finalise an SMS-based intervention to inform the correct use of HIV self-test kits and provide "U = U" "Undetectable = Untransmittable" HIV education for male partners of antenatal women living with HIV. Aim 3: Integrate TENDAI-Together with the SMS-based HIV-self testing intervention and carry out a Phase 2 exploratory trial to test feasibility and acceptability of the integrated intervention. We will recruit 40 women in the 2nd trimester and randomise them, with informed consent, 3:1 to the active intervention (n=30) or enhanced usual care (n=10). We will test the feasibility and acceptability of providing the TENDAI Together intervention with the self-testing SMS platform to allow the woman access to simple care for depression, optimise her engagement in HIV care, and engage her partner with HIVST and subsequent HIV care and prevention steps.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: INFECTION;MENTAL HEALTH
Title: Mental health and HIV among call centre employees in the Philippines: Co-producing a workplace intervention using a systems approach.
Funder: Medical Research Council

Abstract: BACKGROUND: Call centres in the Philippines are the mainstay of their burgeoning business processes outsourcing (BPO) industry. Currently, the Philippines has the fastest growing HIV epidemic in the world and call centre workers are believed to be at an elevated risk. Workplace factors associated with call centres - including high stress and demands, low autonomy, high disposable income in a young workforce, and relatively high proportion of men who have sex with men (MSM) - contribute to this elevated risk. Stigma relating to HIV, sexual behaviour and minority sexual identity, along with stressful working conditions, are known contributors to poor mental health. Workplaces are one of the most important settings for mental health promotion, and offer an entry point for HIV prevention on a wider scale. AIM: To develop a systems-informed workplace intervention to promote mental health and reduce HIV risk among call centre workers in the Philippines. METHODS: Brief scoping review to identify drivers of poor mental and sexual health and select full 'menu' of candidate interventions (organisational, relational and individual components); GIS mapping of local environment 'risk' venues and health facilities; 9 'soft-systems' mapping workshops to identify concepts, relationships, and actors in the workplace system; 6 key informant interviews to understand the wider system (commercial, political, social); evidence synthesis and co-production workshops (6) to agree mechanisms of change and select/refine intervention components; small-scale testing and formative evaluation of intervention components over several cycles. OUTCOMES:An innovative and holistic intervention designed to work across the whole workplace system; plus resources for research on improving the wellbeing of a growing occupational cohort with unique risk factors, and on the methodological and ethical implications of using soft systems methods and co-production approaches within corporate environments.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION;MENTAL HEALTH
Title: Tracking the impact of Covid-19 on the mental health of children, young people and families; follow up of a national longitudinal probability sample
Funder: Medical Research Council

Abstract: Covid-19 led to unprecedented changes to the lives of children and young people. The impact of the pandemic response may delay help-seeking and intervention delivery, widen inequalities, and amplify existing risk factors. Policy-makers and commissioners urgently need longitudinal data on representative populations to guide the mitigation of longer-term impacts at scale. Consequently, we propose broadening the scope of the funded 2020 follow up to the national Mental Health of Children and Young People in England (MHCYP) survey, to include three waves of data collection (June, October, January) and all participants who consented to re-contact. This approach has significant advantages over current convenience surveys, most importantly the use of a well-characterised national probability sample with pre-pandemic baseline data on mental health and risk factors. The aims are: 1/ To track mental health and wellbeing over the course of the pandemic and up to a year afterwards 2/ To identify groups whose mental health may be most adversely affected, and explore risk and protective factors. 3/ To track the impact of and compliance with social distancing measures and school closures on children and families 4/ To examine changes in access to services and support. We will use a combination of online questionnaires and remote semi-structured interviews augmented by health and education data linkages. Content will include child and parent mental health, and impact of covid-19 on education, social and family life. Our output strategy will prioritise rapid dissemination, followed by high impact publications.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: INFECTION;MENTAL HEALTH
Title: Enabling Child and Adolescent Mental Health Services (CAMHS) to provide efficient remote treatment for child anxiety problems in the COVID-19 context
Funder: Medical Research Council

Abstract: This proposal addresses the need for evaluation of innovations in health and social care delivery prompted by the pandemic which can be generalised and actioned in the pandemic context. Specifically this proposal sets out to mitigate the impact of the COVID- 19 outbreak on children, families and Child and Adolescent Mental Health Services (CAMHS) by evaluating an innovative, potentially cost-effective, digital intervention for child anxiety problems. The focus is on child anxiety problems because (i) they are the most common mental health problem across the lifespan, (ii) they typically first occur in childhood and are a common reason for referral to CAMHS, (iii) fears, worries, and anxieties have been fuelled by the current context which has increased perceptions of threat and uncertainty, and (iv) CAMHS have identified children with anxiety problems as a key risk group in the context of COVID-19- both during lockdown and as social distancing measures are relaxed. We will conduct a multi-site randomised non-inferiority trial to establish whether a novel online, parent-led cognitive behavior therapy program (OSI; Online Support and Intervention for child anxiety) is as effective as what CAMHS are currently delivering in the COVID-19 context, and whether it brings health-economic benefits. This research has the potential to provide (i) a solution for efficient psychological treatment for child anxiety disorders while social distancing, (ii) an efficient means of treatment delivery to manage the anticipated increase in CAMHS referrals when social distancing measures are relaxed and schools reopen, and will (iii) pave the way for high quality, efficient evaluation and implementation of digital solutions in CAMHS.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INFECTION;MENTAL HEALTH
Title: The Impact of the COVID-19 Pandemic on People with Severe Mental Illness and on Mental Health Service Provision in South Asia (IMPASS)
Funder: Medical Research Council

Abstract: The COVID-19 pandemic has adversely affected lives and challenged healthcare provision. Those with severe mental illness (SMI; e.g. schizophrenia, bipolar disorder) are likely to be disproportionately affected. Aims & objectives: Investigate impact of the pandemic and its response on people with SMI and on mental health care in Bangladesh and Pakistan. Specifically, for people with SMI, to: a.Explore receipt and response to advice about preventing spread of Covid-19 b.Understand impact on well-being, health, health risk behaviours, quality of life; access to/receipt of mental & physical healthcare; housing and food security, domestic violence, employment, income c.Explore impacts on mental health care d.Inform strategies to mitigate the impact of the pandemic on people with SMI and healthcare services. Methods: Using our existing research collaborations and infrastructure, including a current SMI cohort, we will conduct:1.Quarterly surveys of people with SMI (N=>2K). 2.Semi- structured telephone interviews with patients (N=15-20), families (N=5-10) and mental healthcare workers (N=15-20) in each country. 3.Mental health facility surveys repeated 6- monthly. 4.Joint stakeholder workshops, to present emerging findings, receive feedback and iteratively co-design survey/interview questions, ensuring they are responsive to the evolving pandemic and policy context. Outputs will inform planning to mitigate impact for current and future waves of Covid-19 and other similar epidemics. People with SMI, their families and advocacy organisations will be involved at all stages. We will build capacity in applied research and leadership through experiential learning and training. Impact & dissemination: A Working Group (with patients, families, practitioners and policy makers), and stakeholder workshops will co-produce a targeted, rapid dissemination strategy, including e.g. policy briefs, print/social media, radio/TV and journal articles, using Theory of Change principles.


Research activity codes: 1.2 PSYCHOLOGICAL AND SOCIOECONOMIC PROCESSES
Health categories: INFECTION;MENTAL HEALTH
Title: Understanding and mitigating the psychosocial impact of the COVID-19 pandemic on NHS staff in England
Funder: Medical Research Council

Abstract: The nation has relied heavily on NHS healthcare workers (HCWs) during the COVID-19 pandemic and an effective workforce requires good mental health. Poor quality surveys report high levels of distress in HCWs unconfirmed by some population based studies. So robust evidence is still lacking on the size and impact of the pandemic on HCWs, who is at risk, and what support they may require, if any. We will investigate the psychosocial and occupational outcomes of the pandemic on NHS staff in England, using a well-defined sampling frame across 18 Trusts. Our pilot study, already conducted in three Trusts (Guy's and St Thomas', King's College Hospital, and South London and Maudsley NHS Foundation Trusts) has demonstrated feasibility and acceptability of a brief baseline questionnaire. The original sample will be followed four and eight months later, with 15 new centres contributing data at these timepoints. Questionnaire data will be validated through standardised diagnostic interviews administered by telephone in a sub-sample, to distinguish distress from disorder. Additionally, we will address the use and outcomes of staff support/wellbeing, and a UKRI-funded ethnicity-focused module will capture inequalities in mental health and occupational outcomes. PPI/E will be central: we will establish a steering PPI/E group of NHS workers, unions, and employers, ensuring strong representation of BAME staff. Findings will inform an effective support strategy for NHS staff during and following the pandemic, for example through workforce planning, emergency response strategies, or targeted support. The project team and partners have extensive networks in policy and practice, including NHS-E, allowing for rapid dissemination of findings.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION;MENTAL HEALTH
Title: Evidenced based mental health and wellbeing resources made by young people for young people in the COVID-19 context
Funder: Medical Research Council

Abstract: Young people have faced extensive disruption and challenge throughout the COVID-19 pandemic. There is good evidence to draw on to provide advice and support, but this is often not easily available to young people in accessible and engaging forms. As a joint proposal from the UKRI Emerging Minds and Triumph Networks, and supported by the wider Mental Health Networks, we are uniquely placed to draw on our cross-disciplinary, cross-sector, and lived experience networks to (i) draw together evidence on the mental health and wellbeing impacts of the pandemic on young people, (ii) identify priority areas where resources are needed, (iii) enable young people to develop resources that will be engaging and accessible to young people, and (iv) disseminate the outputs widely. Central aspects of our approach are (a) involvement of young people throughout, including creating opportunities for skills development and training to enable young people to be involved at all stages of designing and developing resources across a range of platforms, including (b) purposeful participation to address the needs of vulnerable groups who are likely to require tailored support and/or may face particular barriers to accessing support, and (c) collaboration with a wide range of partners who will both feed in insights and feed out outputs to ensure that the resources are disseminated widely through sources that young people trust. We are delighted to confirm that we have secured matched funding of £100,000 (Westminster Foundation) to maximise this opportunity to support young people at this unprecedented time.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: INFECTION;MENTAL HEALTH