A5037002335- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Advanced Fluorescence Microscopy Techniques
- Ion Channels and Receptors
- Lipid Membrane Structure and Behavior
- interferon and immune responses
- Plant Stress Responses and Tolerance
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Medicinal Plant Pharmacodynamics Research
- Heat shock proteins research
- CAR-T cell therapy research
- Immune Response and Inflammation
- Image Processing Techniques and Applications
- Protein purification and stability
- Ubiquitin and proteasome pathways
- Nanowire Synthesis and Applications
- GDF15 and Related Biomarkers
- Cancer-related Molecular Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Light effects on plants
Salk Institute for Biological Studies
2012-2023
University of Freiburg
2022
Stanford University
2003-2015
Stanford Medicine
2010
Agilent Technologies (United States)
2010
Howard Hughes Medical Institute
2003-2009
The Honourable Society of Lincoln's Inn
1997-2001
Although much evidence suggests that the plasma membrane of eukaryotic cells is not homogenous, precise architecture this important structure has been clear. Here we use transmission electron microscopy sheets and specific probes to show most or all membrane-associated proteins are clustered in cholesterol-enriched domains ("islands") separated by "protein-free" cholesterol-low membrane. These islands further divided into subregions, as shown localization "raft" "non-raft" markers areas....
Antigen stimulates the dispersion and remodeling of preformed distinct clusters B cell receptors on surface.
T cells become activated when T-cell receptors (TCRs) recognize agonist peptides bound to major histocompatibility complex molecules on antigen-presenting cells. activation critically relies the spatiotemporal arrangements of TCRs plasma membrane. However, molecular organizations lymph node-resident have not yet been determined, owing diffraction limit light. Here we visualized nanometer- and micrometer-scale TCR distributions in nodes by light sheet direct stochastic optical reconstruction...
Significance Immune cell signaling is heavily associated with the spatial organization of molecules. Here, we examined nanoscale coreceptor CD4 and its relative localization to T-cell receptor active form Src kinase p56lck (Lck), using two different superresolution microscopy techniques photoactivated direct stochastic optical reconstruction in both living fixed cells. With concurrent analyses, show that neither CD4/T-cell antigen nor CD4/active Lck nanoclusters colocalize but only overlap...
The T cell receptor (TCR) and associated CD3γε, δε, ζζ signaling dimers allow cells to discriminate between different antigens respond accordingly, but our knowledge of how these parts fit work together is incomplete. In this study, we provide additional evidence that the CD3 heterodimers congregate on one side TCR in both αβ γδTCR-CD3 complexes. We also report other αβTCR mediates homotypic interactions signaling. Specifically, an erythropoietin receptor-based dimerization assay was used...
Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most alleles, peptide binding depends on the catalytic action of human leukocyte antigens (HLA)-DM. HLA-DO selectively expressed in B cells impedes activity DM, yet its physiological role remains unclear. Cell surface iodination assays mass spectrometry II–eluted peptides show that DO affects antigenic repertoire II. generates both quantitative...
Metformin is the front-line treatment for type 2 diabetes worldwide. It acts via effects on glucose and lipid metabolism in metabolic tissues, leading to enhanced insulin sensitivity. Despite significant effort, molecular basis metformin response remains poorly understood, with a limited number of specific biochemical pathways studied date. To broaden our understanding hepatic response, we combine phospho-protein enrichment tissue from genetically engineered mice quantitative proteomics...
Abstract ORAI1 Ca 2+ channels in the plasma membrane (PM) are gated by STIM1 at endoplasmic reticulum (ER)-PM junctions to effect store-dependent entry into cells, but little is known about how local STIM-ORAI signalling coordinated with overall cellular architecture. Filamentous septins can specify cytoskeletal rearrangements and have been found recently modulate signalling. Here we show super-resolution imaging of ORAI1, STIM1, septin 4 living cells that facilitate indirectly. Septin does...
The terminal portion of the Janus kinases (Jaks) contains a divergent FERM ( our‐point‐one, zrin, adixin, oesin) homology domain comprising 19 conserved hydrophobic regions. To determine role this in governing recruitment Jak1, but not Jak3, to gp130 subunit interleukin‐6 family cytokine receptors, interaction three Jak1/Jak3 chimeras with was investigated. Chimeras 1, 2 and 3 (Jak1 regions 1–19, 1–18 1–8/Jak3, respectively) were all enzymically active. 1 interacted cytoplasmic gp130,...
The phosphotyrosine-binding domain of PKCθ interacts with the kinase Zap70 and is required for early TCR signaling.
The kinetics of a ligand-receptor interaction determine the responses receptor-expressing cell. One approach to experimentally and reversibly change this on demand is optogenetics. We have previously developed system in which modified receptor with an engineered ligand can be controlled by light. In soluble Phytochrome B (PhyB) tetramer fused mutated PhyB-interacting factor (PIF S ). However, often natural not soluble, but expressed as membrane protein another This allows interactions two...