A5041110929- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Neuroscience and Neuropharmacology Research
- Photochromic and Fluorescence Chemistry
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Bacterial Genetics and Biotechnology
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Influenza Virus Research Studies
- Cell Adhesion Molecules Research
- Chemical Synthesis and Analysis
- Drug Transport and Resistance Mechanisms
Northwestern University
2021-2025
University of Illinois Urbana-Champaign
2011-2021
University of California, Berkeley
2014-2016
Berkeley College
2015
Howard Hughes Medical Institute
2012
Institute for Advanced Studies in Basic Sciences
2007
The motion of an artificial microscale swimmer that uses a chemical reaction catalyzed on its own surface to achieve autonomous propulsion is fully characterized experimentally. It shown at short times it has substantial component directed motion, with velocity depends the concentration fuel molecules. At longer times, reverts random walk substantially enhanced diffusion coefficient. Our results suggest strategies for designing chemotactic systems.
The classical view of DNA posits that must be stiff below the persistence length [<150 base pairs (bp)], but recent studies addressing this have yielded contradictory results. We developed a fluorescence-based, protein-free assay for studying cyclization single molecules in real time. samples equilibrium population sharply bent, transient species is entirely suppressed single-molecule mechanical measurements and biologically more relevant than annealed sampled traditional ligase-based assay....
Influenza A virus possesses a segmented genome of eight negative-sense, single-stranded RNAs. The segments have been shown to be represented in approximately equal molar ratios population; however, the exact copy number each viral RNA segment per individual particles has not determined. We established an experimental approach based on multicolor single-molecule fluorescent situ hybridization (FISH) study composition RNAs at single-virus particle resolution. Colocalization analysis showed...
It is unclear that how subcellular organelles respond to external mechanical stimuli. Here, we investigated the molecular mechanisms by which force regulates Ca2+ signaling at endoplasmic reticulum (ER) in human mesenchymal stem cells. Without extracellular Ca2+, ER release source of intracellular oscillations induced laser-tweezer-traction plasma membrane, providing a model study stimuli can be transmitted deep inside cell body. This upon stimulation mediated not only support cytoskeleton...
The genomes of influenza A viruses consist eight negative-strand RNA segments. Recent studies suggest that are able to specifically package their segmented into the progeny virions. Segment-specific packaging signals virus RNAs (vRNAs) located in 5' and 3' noncoding regions, as well terminal open reading frames. How these function during genome remains unclear. Previously, we generated a 7-segmented which hemagglutinin (HA) neuraminidase (NA) segments A/Puerto Rico/8/34 were replaced by...
DNA mechanical properties play a critical role in every aspect of DNA-dependent biological processes. Recently high throughput assay named loop-seq has been developed to quantify the intrinsic bendability massive number fragments simultaneously. Using data, we develop software tool, DNAcycP, based on deep-learning approach for cyclizability prediction. We demonstrate DNAcycP predicts with fidelity compared experimental data. an independent dataset from vitro selection enrichment loopable...
Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. The capsid expands after about 10%–25% is packaged. When head full, cuts concatemeric DNA dissociates head. Conformational changes, particularly portal, thought drive these transitions. We found that phage T4 machine highly promiscuous,...
ABSTRACT Adhesion G Protein-Coupled Receptors (aGPCRs) are key cell-adhesion molecules involved in numerous physiological functions. aGPCRs have large multi-domain extracellular regions (ECR) containing a conserved GAIN domain that precedes their seven-pass transmembrane (7TM). Ligand binding and mechanical force applied on the ECR regulate receptor function. However, how communicates with 7TM remains elusive, because relative orientation dynamics of within holoreceptor is unclear. Here, we...
Activation of G protein-coupled receptors (GPCRs) is an allosteric process. It involves conformational coupling between the orthosteric ligand binding site and protein site. Factors that bind at non-cognate sites to alter activation process are classified as modulators represent a promising class therapeutics with distinct modes action. For many receptors, how modulation signaling represented structural level unclear. Here, we developed fluorescence resonance energy transfer (FRET) sensors...
Abstract Transfer of information across membranes is fundamental to the function all organisms and primarily initiated by transmembrane receptors. For many receptors, how ligand sensitivity fine-tuned disease associated mutations modulate receptor conformation allosterically affect are unknown. Here we map activation calcium-sensing (CaSR) - a dimeric class C G protein-coupled (GPCR) responsible for maintaining extracellular calcium in vertebrates. We show that CaSR undergoes unique...
During cell division, precise and regulated distribution of cellular material between daughter cells is a critical step governed by complex biochemical biophysical mechanisms. To achieve this, membraneless organelles condensates often require complete disassembly during mitosis. The principles governing the remain poorly understood. Here, we used physical biology approach to study how properties nucleolus, prominent nuclear organelle in eukaryotic cells, change mitosis across different...
G protein-coupled receptors (GPCRs) are the largest family of membrane in humans. They mediate nearly all aspects human physiology and thus high therapeutic interest. GPCR signaling is regulated space time by receptor phosphorylation. It believed that different phosphorylation states possible for a single receptor, each encodes unique outcomes. Methods to determine status GPCRs critical understanding properties ligands therapeutics. However, common proteomic techniques have provided limited...
RNA polymerase III (Pol III) is responsible for transcribing 5S ribosomal (5S rRNA), tRNAs, and other short non-coding RNAs. Its recruitment to the rRNA promoter requires transcription factors TFIIIA, TFIIIC, TFIIIB. Here, we use cryoelectron microscopy (cryo-EM) visualize S. cerevisiae complex of TFIIIA TFIIIC bound promoter. Gene-specific factor interacts with DNA acts as an adaptor TFIIIC-promoter interactions. We also binding TFIIIB subunits, Brf1 TBP (TATA-box protein), which results in...
Significance Tailed bacteriophages and herpes viruses use powerful molecular machines to package their genomes into a viral capsid using ATP as fuel. Recent biophysical structural studies have provided detailed picture of mechanochemistry DNA packaging. However, little is known about the packaging initiation step owing its transient nature. Here, we reconstituted bacteriophage T4 machine imaged individual events in real time. We discovered that initiations occur bursts through multiple...
Abstract Multi-subunit ring-ATPases carry out a myriad of biological functions, including genome packaging in viruses. Though the basic structures and functions these motors have been well-established, mechanisms ATPase firing motor coordination are poorly understood. Here, using single-molecule fluorescence, we determine that active bacteriophage T4 DNA consists five subunits gp17. By systematically doping with an ATPase-defective subunit selecting single containing precise number or...