A5090918422- SARS-CoV-2 and COVID-19 Research
- Tuberculosis Research and Epidemiology
- Molecular Biology Techniques and Applications
- COVID-19 Clinical Research Studies
- Mycobacterium research and diagnosis
- Diagnosis and treatment of tuberculosis
- interferon and immune responses
- Immune Cell Function and Interaction
- Nasal Surgery and Airway Studies
- SARS-CoV-2 detection and testing
- Gene expression and cancer classification
- Digital Imaging for Blood Diseases
- Immune responses and vaccinations
- Blood groups and transfusion
- Neonatal Respiratory Health Research
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Sinusitis and nasal conditions
- Single-cell and spatial transcriptomics
- Metabolomics and Mass Spectrometry Studies
- Olfactory and Sensory Function Studies
- Influenza Virus Research Studies
- Machine Learning in Bioinformatics
- Virus-based gene therapy research
University College London
2020-2024
Great Ormond Street Hospital
2023-2024
Imperial College London
2019-2023
Medical Research Council
2022-2023
Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in people over 85 years age remains high. Here we investigate differences cellular landscape and function paediatric (<12 years), adult (30–50 years) older (>70 ex vivo cultured nasal epithelial cells response infection SARS-CoV-2. We show that cell tropism SARS-CoV-2, expression ACE2 TMPRSS2 subtypes, differ between groups. While ciliated are viral replication centres...
In early 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle the USA. The epidemic remains uncontrolled, with spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular virological evidence that B3.13 genotype viruses rapidly accumulated adaptations polymerase genes enabled better replication bovine cells, as well cells mammalian species humans pigs. We find several gained evolution these PB2 M631L,...
The airway epithelium is a protective barrier that maintained by the self-renewal and differentiation of basal stem cells. Increasing age principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites pediatric adult donors compared their cellular composition gene expression profile (in laser capture-microdissected whole epithelium,...
Background DAR-901 is an inactivated whole cell tuberculosis booster vaccine, prepared using a new scalable, broth-grown method from the master bank of SRL172, vaccine previously shown to prevent tuberculosis. This study examined whether (a) induces CD4+ T cytokine profiles proposed as correlates protection and (b) has specific vaccine-induced immunological signature compared BCG or placebo. Methods We analysed immune responses 10 recipients, 9 recipients placebo Phase I MDES trial. In that...
Abstract The cytokine interleukin-1β (IL-1β) has pivotal roles in antimicrobial immunity, but also incites inflammatory disease. Bioactive IL-1β is released following proteolytic maturation of the pro-IL-1β precursor by caspase-1. UBE2L3, a ubiquitin conjugating enzyme, promotes ubiquitylation and proteasomal disposal. However, actions UBE2L3 vivo its ligase partners this process are unknown. Here we report that deletion Ube2l3 mice reduces turnover macrophages, leading to excessive mature...
Currently, therapeutics for COVID-19 are limited. To overcome this, it is important that we use physiologically relevant models to reproduce the pathology of infection and evaluate efficacy antiviral drugs. Models airway infection, including a human challenge model or well-defined, disease in vitro systems can help determine key components perpetuate severity disease. Here, briefly review currently being used research drug development.
SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role minimizing viral transmission infection. To develop new strategies for preventing infection, this study aimed to identify proteins that protect against infection saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive COVID-19, before vaccination, between June December 2020. were categorized based on their ability block or...
Summary The airway epithelium is a key protective barrier, the integrity of which preserved by self-renewal and differentiation basal stem cells. Epithelial cells are central to pathogenesis multiple lung diseases. In chronic diseases, increasing age principle risk factor. Few studies have explored differences between epithelial in children adults how function changes during ageing poorly understood. Here, we analyze from homeostatic conditions (laser capture-microdissected whole...
Background Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed. Objective To validate promising technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] existing signatures the detection of active TB in samples obtained from individuals with suspected TB. Design Four substudies, each used biobank collected as part interferon gamma release assay (IGRA)...
ABSTRACT Novel and repurposed antiviral drugs are available for the treatment of coronavirus disease 2019 (COVID-19). However, combinations may be more potent lead to faster viral clearance, but methods screening against respiratory viruses not well established labor-intensive. Here, we describe a time-efficient (72–96 h) simple in vitro drug-sensitivity assay severe acute syndrome 2 (SARS-CoV-2) using standard 96-well plates. We employ different synergy models (zero interaction potency,...
Abstract Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in people over 85 years age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach investigate differences cellular landscape function paediatric (<11y), adult (30- 50y) elderly (>70y) nasal epithelial cells experimentally SARS-CoV-2. Our data reveal that cell subtypes show different tropism SARS-CoV-2,...
Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement Mycobacterium (Mtb)-specific cellular immune signatures by flow cytometry discriminates active from latent infection (LTBI) case-control studies; however, their diagnostic accuracy and clinical utility routine practice unknown.Using nested study design within prospective multicenter cohort patients presenting with suspected...
The mucosal barrier is a primary defence against inhaled pathogens, comprising secretory antibodies which have the potential to block viral entry and neutralise infection. There an ongoing need for greater understanding of immunity SARS-CoV-2 In this study, we investigated IgA through non-invasive saliva sampling healthcare workers. A total 551 samples were collected from staff at Great Ormond Street Children’s Hospital who previously tested positive COVID-19. Participant metadata included...
ABSTRACT The cytokine interleukin-1β (IL-1β) has pivotal roles in antimicrobial immunity, but also incites inflammatory pathology. Bioactive IL-1β is released following proteolytic maturation of the pro-IL-1β precursor by caspase-1 inflammasomes. UBE2L3/UBCH7, a conserved ubiquitin conjugating enzyme, promotes ubiquitylation and proteasomal disposal. However, UBE2L3 actions vivo ligases involved this process are unknown. Here we report that deletion Ube2l3 mice markedly reduces turnover...