A5020949701- interferon and immune responses
- HIV Research and Treatment
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Viral Infections and Immunology Research
- T-cell and B-cell Immunology
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- CRISPR and Genetic Engineering
- Vaccine Coverage and Hesitancy
- Liver Disease Diagnosis and Treatment
- COVID-19 diagnosis using AI
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Atherosclerosis and Cardiovascular Diseases
- Cancer Research and Treatments
- Gastric Cancer Management and Outcomes
- COVID-19 and healthcare impacts
Hubei University
2025
Royal Free London NHS Foundation Trust
2023
University College London
2023
University of Cambridge
2018-2021
Medical Research Council
2018-2021
MRC Laboratory of Molecular Biology
2018-2021
Addenbrooke's Hospital
2018-2021
Osaka University
2018
Huazhong University of Science and Technology
2010-2011
Tongji Hospital
2010-2011
TRIM5 is a RING domain E3 ubiquitin ligase with potent antiretroviral function. assembles into hexagonal lattice on retroviral capsids, causing envelopment of the infectious core. Concomitantly, initiates innate immune signaling and orchestrates disassembly viral particle, yet how these antiviral responses are regulated by capsid recognition unclear. We show that assembly triggers N-terminal polyubiquitination collectively drives responses. In uninfected cells, monoubiquitination...
Cell surface Fc receptors activate inflammation and are tightly controlled to prevent autoimmunity. Antibodies also simulate potent immune signalling from inside the cell via cytosolic antibody receptor TRIM21, but how this is regulated unknown. Here we show that TRIM21 constitutively repressed by its B-Box domain activated phosphorylation. The occupies an E2 binding site on catalytic RING mimicking E2-E3 interactions, inhibiting ubiquitination preventing activation. derepressed IKKβ TBK1...
Abstract The cytosolic antibody receptor TRIM21 possesses unique ubiquitination activity that drives broad-spectrum anti-pathogen targeting and underpins the protein depletion technology Trim-Away. This is dependent on formation of self-anchored, K63-linked ubiquitin chains by heterodimeric E2 enzyme Ube2N/Ube2V2. Here we reveal how facilitates transfer differentiates this from other closely related enzymes. A tri-ionic motif provides optimally distributed anchor points allow to wrap an...
NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in target-based assay as an inhibitor of interaction between HIV-1 (ψ) stem-loop 3 (SL3) RNA and Gag. This shown to exhibit potent antiviral activity. Here, effects this on individual stages viral lifecycle were examined by qRT-PCR, ELISA Western blot, see if its actions specific packaging stage. The structural NSC260594 binding gRNA also SHAPE dimerization assays. Treatment cells...
The genetic basis of most human disease cannot be explained by common variants. One solution to this ‘missing heritability problem’ may rare missense variants, which are individually scarce but collectively abundant. However, the phenotypic impact variants is under-appreciated as gene function normally studied in context a single ‘wild-type’ sequence. Here, we explore naturally occurring population on cytosolic antibody receptor TRIM21, using volunteer cells with variant haplotypes, CRISPR...
The National Health Service (NHS) in England commissioned opt-out testing London Emergency Departments (ED) April 2022 to allow early identification and management of hepatitis B (HBV) C virus (HCV) infection patients unaware their status.
HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both and their native RNA structure are essential for virion infectivity. The precise stepwise nature packaging process has not been resolved. This is largely due to a prior lack techniques that follow changes within RNA–protein complex. Here, we apply in-gel SHAPE (selective 2’OH acylation analysed by primer extension) technique study initiation packaging, examining between signal...
SUMMARY Trim-Away is a powerful new technology that exploits off-the-shelf antibodies and the E3 RING ligase cytosolic antibody receptor TRIM21 to carry out rapid protein depletion. How catalytically-activated upon substrate engagement during either its normal immune function or when re-purposed for targeted degradation unknown. Here we show mechanism of substrate-induced clustering triggers intermolecular dimerization domain switch on ubiquitination activity induce an antiviral response...
Objective To study the effects of protein kinase A (PKA) phosphorylation site' s mutation mitofusin-2 (Mfn2) on intimal proliferation after balloon injury carotid artery rats. Method Rat model was established and infected with Adv-LacZ, Adv-Mfn2, AdvMfn2-S442A or Adv-Mfn2-S442D from peri-arterial sheathes vessels, while phosphate buffered solution (PBS) used instead above infectious adenovirus as uninfected group sham operation control group. The rats were sacrificed 14 days in order to...