A5018535086- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Bioinformatics and Genomic Networks
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Immune responses and vaccinations
- Computational Drug Discovery Methods
- Advanced Biosensing Techniques and Applications
- Genetic Associations and Epidemiology
- Chemokine receptors and signaling
- Breast Cancer Treatment Studies
- Cardiomyopathy and Myosin Studies
- HER2/EGFR in Cancer Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Redox biology and oxidative stress
Institute of Structural and Molecular Biology
2023-2025
University College London
2023-2025
Birkbeck, University of London
2025
King's College London
2018-2024
Guy's Hospital
2020
British Heart Foundation
2020
St Thomas' Hospital
2020
HKU-Pasteur Research Pole
2016
University of Hong Kong
2016
Separation of B cells into different subsets has been useful to understand their functions in various immune scenarios. In some instances, the defined by phenotypic FACS separation are relatively homogeneous and so establishing associated with them is straightforward. Other subsets, such as “Double negative” (DN, CD19+CD27-IgD-) population, more complex reports differing functionality which could indicate a heterogeneous population. Recent advances single-cell techniques enable an...
Abstract In breast cancer, humoral immune responses may contribute to clinical outcomes, especially in more immunogenic subtypes. Here, we investigated B lymphocyte subsets, immunoglobulin expression, and clonal features tumors, focusing on aggressive triple-negative cancers (TNBC). samples from patients with TNBC healthy volunteers, circulating tumor-infiltrating lymphocytes (TIL-B) were evaluated. CD20+CD27+IgD− isotype-switched increased compared matched blood. TIL-B frequently formed...
Abstract Metabolic programming is important for B cell fate, but the bioenergetic requirement regulatory (B reg ) differentiation and function unknown. Here we show that differentiation, unlike non-B cells, relies on mitochondrial electron transport homeostatic levels of reactive oxygen species (ROS). Single-cell RNA sequencing analysis revealed TXN , encoding metabolic redox protein thioredoxin (Trx), highly expressed by Trx inhibitor TXNIP which was downregulated. Pharmacological...
APOBEC3 cytidine deaminases are largely known for their innate immune protection from viral infections. Recently, members of the family have been associated with a distinct mutational activity in some cancer types. We report pan-tissue, pan-cancer analysis RNA-seq data specific to genes 8,951 tumours, 786 cell lines and 6,119 normal tissues. By deconvolution levels different types tumour admixtures, we demonstrate that APOBEC3B (A3B), primary candidate as mutagen, shows little association...
B cells are known to contribute the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized these cancers detail. Here we show comprehensive phenotyping samples of circulating and tumor-resident well serum antibodies melanoma patients. Memory enriched compared blood paired feature distinct antibody repertoires, linked specific isotypes. Tumor-associated undergo clonal expansion, class switch recombination, somatic...
Class-switch recombination (CSR) is an integral part of B cell maturation. Here we present sciCSR (pronounced 'scissor', single-cell inference class-switch recombination), a computational pipeline that analyzes CSR events and dynamics cells from RNA sequencing (scRNA-seq) experiments. Validated on both simulated real data, re-analyzes scRNA-seq alignments to differentiate productive heavy-chain immunoglobulin transcripts germline 'sterile' transcripts. From snapshot Markov state model built...
Nowadays, it is possible to combine X-ray crystallography and fragment screening in a medium throughput fashion chemically probe the surfaces used by proteins interact use outcome of screens systematically design protein-protein inhibitors. To prove it, we first performed bioinformatics analysis Protein Data Bank protein complexes, which revealed over 400 cases where crystal lattice target free form such that large portions interacting are from contacts therefore accessible fragments during...
Abstract Summary We present TITINdb2, an update to the TITINdb database previously constructed facilitate identification of pathogenic missense variants in giant protein titin, which are associated with a variety skeletal and cardiac myopathies. The web portal have been substantially revised include following new features: (i) increase computational annotation from 4 20 variant impact predictors, available through custom data table dialogue; (ii) thorough structural coverage single domains...
Missense variants are present amongst the healthy population, but some of them causative human diseases. A classification associated with “healthy” or “diseased” states is therefore not always straightforward. deeper understanding nature missense in health and disease, cellular processes they may affect, general molecular principles which underlie these differences essential to offer mechanistic explanations true impact pathogenic variants. Here, we have formalised a statistical framework...
The development of stable antibodies formed by compatible heavy (H) and light (L) chain pairs is crucial in both the vivo maturation antibody-producing cells ex designs therapeutic antibodies. We present here a novel machine learning framework, ImmunoMatch, for deciphering molecular rules governing pairing antibody chains. Fine-tuned on an antibody-specific language model, ImmunoMatch learns from paired H L sequences single human B to distinguish cognate H-L randomly sequences. find that...
Artificial intelligence and machine learning models have been developed to engineer antibodies for specific recognition of antigens, however these approaches often focus on the antibody complementarity determining region (CDR) whilst ignoring immunoglobulin framework (FW) which provides structural rigidity support flexible CDR loops. Here we present an integrated computational-experimental workflow, combining static structure analyses, molecular dynamics simulations in vitro physicochemical...
Class switch recombination (CSR) allows the formation of functionally specialized antibodies. Understanding CSR dynamics is key for better design and prediction vaccines to protect mucosal surfaces. To investigate in a primary human immune response under controlled setting, we sampled healthy volunteers without COVID-19 history every other day during first three weeks after SARS-CoV-2 vaccination, with additional time points up six months. Leveraging bulk single-cell B cell receptor...
Immunoglobulin gene heterogeneity reflects the diversity and focus of humoral immune response towards different infections, enabling inference B cell development processes. Detailed compositional lineage analysis long read IGH repertoire sequencing, combining examples pandemic, epidemic endemic viral infections with control vaccination samples, demonstrates general responses including increased use
People for and against direct-to-consumer (DTC) genomic tests are arguing around two issues: first, on whether an autonomy-based account can justify the tests; second, bring any personal utility. Bunnik et al, in article published this journal, were doubtful latter, especially clinically irrelevant uninterpretable sequences, how far claim could go justification. Here we argue that utility is inherent to DTC their results. We discuss al's of identify problems its motivation application. then...
Loose anagen hair is a rare form of impaired anchorage in which hairs that lack inner and outer root sheaths can be gently painlessly plucked from the scalp. This condition usually occurs children often self-limiting. A genetic basis for disorder has been suggested but not proven. better understanding aetiology loose may improve prevention treatment strategies.To identify possible using next-generation DNA sequencing functional analysis variants identified.In this case study, whole-exome...
In-crystal fragment screening is a powerful tool to chemically probe the surfaces used by proteins interact, and identify chemical space worth exploring design protein-protein inhibitors. A crucial prerequisite identification of crystal form where target area exposed accessible be probed fragments. Here we report SARS-CoV-2 Receptor Binding Domain in complex with CR3022 antibody ACE2 binding site on accessible. This valuable develop antiviral molecules that could act blocking virus entry cells.
Abstract Sustainable modern poultry production depends on effective protection against infectious diseases and a diverse range of antibodies is key for an immune response. In the domestic chicken, somatic gene conversion dominant process in which antibody immunoglobulin genes are diversified. Affinity maturation by hypermutation (SHM) also occurs, but relative contribution versus to (Ig) diversity poorly understood. this study, we use high throughput long-read sequencing study multiple...
Generalized pustular psoriasis (GPP) is a potentially life-threatening skin disease, associated with IL36RN mutations. encodes the interleukin (IL)-36 receptor antagonist (IL-36Ra), protein that downregulates activity of IL-36 cytokines by blocking their (IL-36R). While GPP can be treated IL-36R inhibitors, structural underpinnings IL-36Ra/IL-36R interaction remain poorly understood. Here, we sought to address this question systematically investigating effects mutations.We experimentally...
The mechanisms of B-cell diversification differ greatly between aves and mammals, but both produce B cells antibodies capable supporting an effective immune response. To see how differences in the generation diversity might affect overall repertoire diversity, we have compared characteristics immunoglobulin genes from domestic chickens to those humans. Both use V(D)J gene rearrangement somatic hypermutation, only conversion. A range analysis tools were used investigate multiple aspects amino...
Abstract Class-switch recombination (CSR) is an integral part of B cell maturation. Steady-state analyses isotype distribution (e.g. receptor [BCR] repertoire analysis snapshots during immune response) do not directly measure CSR dynamics, which crucial in understanding how maturation regulated across time. We present sciCSR (pronounced ‘scissor’, single-cell inference class switch recombination), a computational pipeline events and dynamics cells from RNA-sequencing (scRNA-seq) experiments....
Human APOBEC3 (A3; apolipoprotein B mRNA editing catalytic polypeptide-like 3) is a family of seven enzymes involved in generating mutations nascent reverse transcripts many retroviruses, as well the human genome range cancer types. The structural details interaction between A3 proteins and DNA molecules are only available for few members. Here we use homology modelling techniques to address difference coverage interacting with different substrates. A3-DNA interfaces represented residue...