A5039782330- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Micro and Nano Robotics
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Pancreatic function and diabetes
- Ion channel regulation and function
- Protist diversity and phylogeny
- Erythrocyte Function and Pathophysiology
- Protein Structure and Dynamics
- Advanced Fluorescence Microscopy Techniques
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- SARS-CoV-2 detection and testing
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Microfluidic and Bio-sensing Technologies
- Cellular Mechanics and Interactions
- Single-cell and spatial transcriptomics
- Cancer Mechanisms and Therapy
- Electron Spin Resonance Studies
The Ohio State University
2024
University of California, San Francisco
2019-2022
Howard Hughes Medical Institute
2019-2022
University of California, Berkeley
2013-2020
University of Maryland, College Park
2009-2014
Berkeley College
2013-2014
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the cell receptor angiotensin-converting enzyme (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt ACE2. Cryo-electron microscopy (cryo-EM) revealed one nanobody, Nb6, binds in fully inactive conformation with binding domains locked into their inaccessible down state, incapable...
Protein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) an ER membrane-resident kinase/RNase that mediates signal transmission most evolutionarily conserved branch of UPR. Dimerization and/or higher-order oligomerization IRE1 are thought to be important for its activation mechanism, yet actual oligomeric states inactive, active, and attenuated mammalian complexes remain...
Significance The endoplasmic reticulum (ER) is the site for folding and maturation of secreted membrane proteins. When ER protein-folding machinery overwhelmed, misfolded proteins trigger stress, which frequently linked to human diseases, including cancer neurodegeneration. Inositol-requiring enzyme 1 (IRE1) an membrane-resident sensor that assembles into large clusters previously unknown organization upon its activation by unfolded peptides. We demonstrate IRE1 are topologically complex...
Mechanosensitive channel of small conductance (MscS), a tension-driven osmolyte release valve residing in the inner membrane Escherichia coli, exhibits complex adaptive behavior, whereas its functional counterpart, mechanosensitive large (MscL), was generally considered nonadaptive. In this study, we show that both channels exhibit similar adaptation excised patches, process is completely separable from inactivation prominent only MscS. When patch held under constant pressure, manifested as...
ABSTRACT Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. gains entry into host cells via interaction between its Spike protein the cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this confers potent neutralization viral entry, providing avenue for vaccine design therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt ACE2. By screening...
The mechanosensitive channel of small conductance (MscS) is a bacterial tension-driven osmolyte release valve with homologues in many walled eukaryotic organisms. When stimulated by steps tension excised patches, Escherichia coli MscS exhibits transient opening followed reversible adaptation and then complete inactivation. Here, we study properties the inactivation transition, which renders nonconductive insensitive. Using special pressure protocols demonstrate that are sequential processes...
Mitochondrial function depends crucially on the maintenance of multiple mitochondrial DNA (mtDNA) copies. Surprisingly, cellular mechanisms regulating mtDNA copy number remain poorly understood. Through a systematic high-throughput approach in Saccharomyces cerevisiae, we determined mtDNA-to-nuclear ratios 5148 strains lacking nonessential genes. The screen revealed MRX6, largely uncharacterized gene, whose deletion resulted marked increase levels, while maintaining wild type-like structure...
The mitochondrial AAA ( A TPase ssociated with diverse cellular ctivities) protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well stuck import substrates from the outer membrane, facilitating their re-insertion into cognate organelles and maintaining mitochondria’s capacity. In doing so, it helps to maintain proteostasis mitochondria. How tackles energetic challenge extract hydrophobic proteins lipid bilayer what structural features adapt for its particular...
Abstract Tracking single molecules inside cells reveals the dynamics of biological processes, including receptor trafficking, signalling and cargo transport. However, individual often cannot be resolved due to their high density. Here we develop PhotoGate technique that controls number fluorescent particles in a region interest by repeatedly photobleaching its boundary. bypasses requirement photoactivation track at surface densities two orders magnitude greater than single-molecule detection...
Abstract Protein folding homeostasis in the endoplasmic reticulum (ER) is regulated by a signaling network, termed unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) an ER membrane-resident kinase/RNase that mediates signal transmission most evolutionarily conserved branch of UPR. Dimerization and/or higher-order oligomerization IRE1 are thought to be important for its activation mechanism, yet actual oligomeric states inactive, active, and attenuated mammalian complexes...
Abstract The mitochondrial AAA protein ATAD1 (in humans; Msp1 in yeast) removes mislocalized membrane proteins, as well stuck import substrates from the outer membrane, facilitating their re-insertion into cognate organelles and maintaining mitochondria’s capacity. In doing so, it helps to maintain proteostasis mitochondria. How tackles energetic challenge extract hydrophobic proteins lipid bilayer what structural features adapt for its particular function has remained a mystery. Previously,...