- Receptor Mechanisms and Signaling
- Advanced Electron Microscopy Techniques and Applications
- Psychedelics and Drug Studies
- Chemical synthesis and alkaloids
- Electron and X-Ray Spectroscopy Techniques
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Monoclonal and Polyclonal Antibodies Research
- Force Microscopy Techniques and Applications
- Protein Structure and Dynamics
- Phosphodiesterase function and regulation
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Molecular Junctions and Nanostructures
- Protein Kinase Regulation and GTPase Signaling
- Photoreceptor and optogenetics research
- Human Health and Disease
- Dermatologic Treatments and Research
- Calcium signaling and nucleotide metabolism
- Natural Compound Pharmacology Studies
- Neuroendocrine regulation and behavior
Stanford University
2020-2024
Melbourn Science Park
2022-2023
Lawrence Berkeley National Laboratory
2016-2019
University of California, Berkeley
2016-2019
Central Clinical Hospital and Polyclinic
2005
Changes in lattice structure across sub-regions of protein crystals are challenging to assess when relying on whole crystal measurements. Because this difficulty, macromolecular determination from micro and nanocrystals requires assumptions bulk crystallinity domain block substructure. Here we map micron size areas cryogenically preserved three-dimensional peptide using a nano-focused electron beam. This approach produces diffraction as few 1500 molecules crystal, is sensitive thickness...
Human cytomegalovirus (HCMV) encodes G protein–coupled receptors (GPCRs) US28 and US27 , which facilitate viral pathogenesis through engagement of host proteins. Here we report cryo–electron microscopy structures forming nonproductive productive complexes with Gi Gq, respectively, exhibiting unusual features functional implications. The “orphan” GPCR lacks a ligand-binding pocket has captured guanosine diphosphate–bound inactive tenuous interaction. docking modes CX3CL1-US28 to favor...
Summary G protein-coupled receptors (GPCRs) activate heterotrimeric proteins by stimulating the exchange of guanine nucleotide in Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines progression ensembles pre-steady-state intermediates GPCR-G protein complex. Using variability analysis to monitor transitions stimulatory Gs complex with β 2 -adrenergic receptor (β AR) at short sequential time points after GTP addition, identified conformational...
Summary Cryogenic electron microscopy (cryo-EM) has widened the field of structure-based drug discovery by allowing for routine determination membrane protein structures previously intractable. However, despite representing one largest classes therapeutic targets, most inactive-state G protein-coupled receptors (GPCRs) have remained inaccessible cryo-EM because their small size and membrane-embedded nature impedes projection alignment high-resolution map reconstructions. Here we demonstrate...
We have developed low dose diffraction mapping techniques for application to beam sensitive materials [1].By exposing the sample with a controlled of incident electrons, from crystalline regions is captured and used create contrast in an image reconstructed 4-dimensional dataset.These are applied model polyethylene (PE) as well precise acid-containing [2] poly 3-hexylthiophene (P3HT) [3], conjugated semiconducting polymer organic electronic devices.TEM acquisition parameters such probe size...