A5024862429- CAR-T cell therapy research
- Microtubule and mitosis dynamics
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Nanowire Synthesis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- SARS-CoV-2 and COVID-19 Research
- Genetic and Kidney Cyst Diseases
- Immune Cell Function and Interaction
- Cellular transport and secretion
- SARS-CoV-2 detection and testing
- Advancements in Semiconductor Devices and Circuit Design
- DNA Repair Mechanisms
- Lymphoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Advanced Fluorescence Microscopy Techniques
- Acute Lymphoblastic Leukemia research
- Advanced Electron Microscopy Techniques and Applications
- Immunotherapy and Immune Responses
Autolus (United Kingdom)
2017-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015-2017
Centre National de la Recherche Scientifique
2005-2017
Institut de Biosciences et Biotechnologies
2017
Université Grenoble Alpes
2016-2017
Hôpital Saint-Louis
2017
Université Paris Cité
2017
Ecotaxie, Microenvironnement et développement lymphocytaire
2017
CEA Grenoble
2015-2016
Inserm
2016
Objective To determine the distribution of interleukin-10 (IL-10) 5′ flanking region haplotypes in children with arthritis and controls, to investigate functional significance each haplotype. Methods Sequence-specific oligonucleotide probing was used haplotype frequency. Transient transfection studies were transcription reporter genes driven by Whole blood cultures performed assess IL-10 production genotype. Results Patients involving >4 joints more likely have a genotype an ATA than those...
The centrosome organizes microtubules by controlling nucleation and anchoring processes. In mammalian cells, subdistal appendages of the mother centriole are major microtubule-anchoring structures centrosome. It is not known how newly nucleated anchored to these appendages. We show here that ninein, a component appendages, localizes via its C-terminus interacts with gamma-tubulin-containing complexes N-terminus. Expression construct encoding ninein displaced endogenous gamma-tubulin ring...
Microtubule nucleation is the best known function of centrosomes. Centrosomal microtubule mediated primarily by gamma tubulin ring complexes (gamma TuRCs). However, little about molecules that anchor these to In this study, we show centrosomal coiled-coil protein pericentrin anchors TuRCs at spindle poles through an interaction with complex proteins 2 and 3 (GCP2/3). Pericentrin silencing small interfering RNAs in somatic cells disrupted localization organization mitosis but had no effect on...
Centrosomes nucleate microtubules and contribute to mitotic spindle organization function. They also participate in cytokinesis cell cycle progression ways that are poorly understood. Here we describe a novel human protein called centriolin localizes the maternal centriole functions both progression. Centriolin silencing induces failure by mechanism whereby cells remain interconnected long intercellular bridges. Most continue cycle, reenter mitosis, form multicellular syncytia. Some...
Abstract Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits efficacy immunotherapeutic approaches. The receptor expresses one two highly homologous chains [T β-chain constant (TRBC) domains 1 and 2] in mutually exclusive manner, making it promising target. Here we demonstrate specificity redirection by rational design using structure-guided...
Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is key regulator of this process whose activity essential for centriole duplication. Here, we show that PLK4 autophosphorylation serine S305 consequence activation and enables the active fraction to be identified cell. Active detectable on replicating mother G1/S, with proportion increasing through interphase reach maximum mitosis. Activation at daughter delayed until G2, but level...
Summary Primary cilium formation is initiated at the distal end of mother centriole in a highly co-ordinated manner. This requires capping with ciliary vesicle and anchoring basal body (mother centriole) to cell cortex, both which are mediated by appendages. Here, we show that appendage protein Cep123 (Cep89/CCDC123) required for assembly, but not maintenance, primary cilium. In absence fails, suggesting it functions early stages ciliogenesis. Consistent such role, interacts centriolar...
The structure of the centrosome was resolved by EM many years ago to reveal a pair centrioles embedded in dense network proteins. More recently, molecular composition catalogued mass spectroscopy and novel components were identified. Determining precisely where component localizes within remains challenge, until now it has required use immuno-EM. This technique is both time-consuming unreliable, as often fails due problems with antigen accessibility. We have investigated two nanoscopic...
Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to apical surface, yet surprisingly little known about this initiating step. To gain insight into mechanisms driving migration, we exploited reproducibility of architecture on adhesive micropatterns investigate cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with transient formation an array cold-stable microtubules, actin cytoskeleton...
CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL DLBCL. However, loss is a frequent cause of relapse. Simultaneously targeting second antigen, CD22, may decrease antigen escape, but challenging: its density approximately 10-fold less than CD19, large structure hamper immune synapse formation. The characteristics the optimal CD22 are underexplored. We generated 12 distinct antibodies tested CARs derived from them to identify based on novel 9A8 antibody, which was...
Polo-like kinase 4 (PLK4) is a unique member of the family kinases that shares little homology with its siblings and has an essential role in centriole duplication. The turn-over this must be strictly controlled to prevent amplification. This achieved, part, by autoregulatory mechanism, whereby PLK4 autophosphorylates residues PEST sequence located carboxy-terminal catalytic domain. Phosphorylated subsequently recognized SCF complex, ubiquitinylated targeted proteasome for degradation....
The human angiotensin-converting enzyme 2 acts as the host cell receptor for SARS-CoV-2 and other members of Coronaviridae family SARS-CoV-1 HCoV-NL63. Here, we report biophysical properties spike variants D614G, B.1.1.7, B.1.351, P.1 with affinities to ACE2 infectivity capacity, revealing weaknesses in developed neutralizing antibody approaches. Furthermore, a preclinical characterization package soluble decoy engineered be catalytically inactive immunologically inert, broad neutralization...
Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2beta). CHD4 part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show many NuRD components interacted by coimmunoprecipitation they localized centrosomes midbodies. Overexpression pericentrin-binding domain or another family member (CHD3)...
A versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component based on the disruption of protein–protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent biodistribution, low toxicity. The comprises anti-minocycline single-domain antibody (sdAb) minocycline-displaceable cyclic peptide. Here, show how this versatile can be applied to OFF-switch split...
Phage display technology in combination with next-generation sequencing (NGS) currently is a state-of-the-art method for the enrichment and isolation of monoclonal antibodies from diverse libraries. However, current NGS methods employed phage libraries are limited by short contiguous read lengths associated second-generation platforms. Consequently, identification antibody sequences has conventionally been restricted to individual domains or analysis single domain binding moieties such as...
Adoptive T-cell therapy aims to achieve lasting tumor clearance, requiring enhanced engraftment and survival of the immune cells. Cytokines are paramount modulators proliferation. Cytokine receptors signal via ligand-induced dimerization, this principle has been hijacked utilizing nonnative dimerization domains. A major limitation current technologies resides in absence a module that recapitulates natural cytokine receptor heterodimeric pairing. To circumvent this, we created new engineered...
Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into genome without generating detrimental DNA double-stranded breaks. Base-editing enzymes are commonly delivered in form modified linear messenger RNA (mRNA) that costly to produce. Here, we address this problem by developing simple protocol for manufacturing base-edited cells using circular (circRNA), which less expensive synthesize. Compared with mRNA, higher efficiencies were achieved...
Arfaptin2 contains a Bin/Amphiphysin/Rvs (BAR) domain and directly interacts with proteins of the Arf/Arl family in their active GTP-bound state. It has been proposed that BAR domains are able to sense membrane curvature induce tubulation. We report here Arf1 is required for recruitment artificial liposomes mimicking Golgi apparatus lipid composition. The Arf1-dependent increases curvature, while itself not sensitive curvature. At high protein concentrations, binding induces Finally,...
The hostile tumor microenvironment limits the efficacy of adoptive cell therapies. Activation Fas death receptor initiates apoptosis and disrupting these receptors could be key to increasing CAR T efficacy. We screened a library Fas-TNFR proteins identifying several novel chimeras that not only prevented ligand-mediated kill, but also enhanced by signaling synergistically with CAR. Upon binding ligand, Fas-CD40 activated NF-κB pathway, inducing greatest proliferation IFN-γ release out all...
Abstract When the TCR binds Ag it is phosphorylated, internalized, and degraded. We wished to examine whether this process was accompanied by a specific concomitant increase in mRNA levels. To do this, PBMC T cell clone were cultured with series of superantigens an alloantigen. Only cells specifically responding antigenic stimulus had increased levels β-chain variable (TCRBV)-specific mRNA. This response apparent after 48 h, peaked around 72 still elevated 7 days. Increased gene...
SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs ITSMs on immune receptors. Consequently, key in the transmission of signals within T cells, constituting an important point convergence for diverse Therefore, inhibition may represent a strategy preventing immunosuppression cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both contain dual domains responsible...