A5058111270- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- CAR-T cell therapy research
- Bacterial Genetics and Biotechnology
- Animal Virus Infections Studies
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- RNA regulation and disease
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- SARS-CoV-2 detection and testing
- Histiocytic Disorders and Treatments
- Hematopoietic Stem Cell Transplantation
- vaccines and immunoinformatics approaches
- Hepatitis C virus research
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
Max Delbrück Center
2015-2024
University of Cologne
2020-2023
University Hospital Cologne
2020-2023
Heinrich Heine University Düsseldorf
2019-2020
Forschungszentrum Jülich
2019
Wellcome Centre for Mitochondrial Research
2018
University of Newcastle Australia
2018
Newcastle University
2018
The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs vaccines are limited or not available, new options COVID-19 treatment prevention in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed antibody response of 12 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, isolated 255 antibodies different time points as early Of these, 27 potently neutralized...
The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In particular, Rosa26 knock-in alleles the insertion transgenes a genomic 'safe harbor' site, have not been produced. Here we applied 8–11 kb inserts into C57BL/6 zygotes. We found that 10–20 % live pups derived from microinjected zygotes were founder mutants, without apparent off-target effects, up to 50 recovered upon...
Significance Efficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-mediated mutagenesis is necessary for robust genetic screening in primary cells and requires sufficiently high levels of Cas9 reliable single guide RNAs (sgRNAs). We provide a sgRNA design tool that selects high-fidelity sgRNAs transgenic mouse line expresses at all analyzed. Using this system, we achieved an average knockout efficiency 80% B established...
Bacteriocins are toxic polypeptides made by bacteria to kill their competitors, making them interesting as potential antibiotics. Here, we reveal unsuspected commonalities in bacteriocin uptake pathways, through molecular and cellular dissection of the import pathway for pore-forming pyocin S5 (PyoS5), which targets Pseudomonas aeruginosa . In addition its C-terminal domain, PyoS5 is composed two tandemly repeated helical domains that also identify other pyocins. Functional analyses...
The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond repeated antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory cell pool. We demonstrate that subsequent infection substantially increases frequency encoding SARS-CoV-2-neutralizing antibodies. However, this is not primarily attributable maturation, but selection preexisting clones....
Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, often fatal immune deficiency characterized by severe systemic hyperinflammation. Although allogeneic bone marrow transplantation can be curative, more effective therapies are urgently needed. FHL caused inactivating mutations in proteins that regulate cellular immunity. Here, we used adeno-associated virus–based CRISPR-Cas9 system with inhibitor of nonhomologous end joining to repair such potentially long-lived T cells ex...
The blueprints of developing organs are preset at the early stages embryogenesis. Transcriptional and epigenetic mechanisms proposed to developmental trajectories. However, we reveal that competence for future cardiac fate human embryonic stem cells (hESCs) is in pluripotency by a specialized mRNA translation circuit controlled RBPMS. RBPMS recruited active ribosomes hESCs control essential factors needed commitment program, including Wingless/Integrated (WNT) signaling. Consequently, loss...
Significance Epstein–Barr Virus infects human B cells and drives them into proliferation transformation. Although more than 90% of the population is EBV-infected, EBV-driven pathologies including B-cell lymphomas are limited by a potent T-cell immune response. Here, we present mouse model for acute EBV infection through conditional expression two key proteins, LMP1 LMP2A. This reproduces expansion, T-cell–mediated surveillance EBV-infected cells, fatal lymphoproliferative disease when...
Epstein-Barr virus (EBV) is a B cell transforming that causes malignancies under conditions of immune suppression. EBV orchestrates transformation through its latent membrane proteins (LMPs) and nuclear antigens (EBNAs). We here identify secondary mutations in mouse lymphomas induced by LMP1, to predict key functions other genes during transformation. find aberrant activation early factor 1 (EBF1) promote LMP1-expressing cells inhibiting their differentiation plasma cells. EBNA3A phenocopies...
SUMMARY The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and world economy. Since approved drugs vaccines are not available, new options COVID-19 treatment prevention highly demanded. To identify neutralizing antibodies, we analysed the antibody response of 12 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, isolated 255 antibodies different time points as early Among these, 28 potently neutralized authentic (IC...
Abstract The germinal center reaction is essential for efficient humoral immunity, but it can also give rise to B cell lymphomas. Cre/loxP‐mediated conditional gene knock‐out or knock‐in be used the genetic manipulation of cells in vivo. Here we present a novel allele, Cγ1‐CreERT2, that allows timed activation Cre recombinase small fraction cells. This allele will useful study normal and malignant development
Most people infected by EBV acquire specific immunity, which then controls latent infection throughout their life. Immune surveillance of EBV-infected cells cytotoxic CD4+ T has been recognized; however, the molecular mechanism generating effector subset remains poorly understood. Here we compared phenotypic features and transcriptome EBV-specific effector-memory CD8+ in mice found that both cell types show cytotoxicity and, to our surprise, widely similar gene expression patterns relating...
Abstract Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation differentiation HSPCs are regulated complex transcriptional networks. In order to identify transcription factors with key roles HSPC-mediated reconstitution, we developed an efficient robust CRISPR/Cas9-based vivo genetic screen. Using this experimental system, identified TFDP1 factor be essential for HSPC proliferation...
SUMMARY Somatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2 neutralizing antibodies. Yet, several potent antibodies carry no or only few mutations, leaving the question of how ongoing SHM affects neutralization. Here, we reverted variable region mutations 92 tested their impact on binding Reverting higher numbers correlated with decreasing antibody functionality. However, some antibodies, including public clonotype VH1-58, remained unaffected for...
Abstract Pyocin S5 (PyoS5) is a potent protein bacteriocin that eradicates the human pathogen P. aeruginosa in animal infection models, but its import mechanism poorly understood. Here, using crystallography, biophysical and biochemical analysis live-cell imaging, we define entry process of PyoS5 reveal links to transport mechanisms other bacteriocins. In addition C-terminal pore-forming domain, elongated comprises two novel tandemly repeated kinked three helix bundle domains structure-based...