A5027746139- Diffusion and Search Dynamics
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Photoreceptor and optogenetics research
- DNA and Nucleic Acid Chemistry
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Force Microscopy Techniques and Applications
- Lipid Membrane Structure and Behavior
- Gene Regulatory Network Analysis
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neuropharmacology Research
- Molecular Communication and Nanonetworks
- Autophagy in Disease and Therapy
- ATP Synthase and ATPases Research
- Spectroscopy and Quantum Chemical Studies
- Bacteriophages and microbial interactions
- Micro and Nano Robotics
- Epigenetics and DNA Methylation
- Microfluidic and Bio-sensing Technologies
- Protein Structure and Dynamics
University of California, San Diego
2016-2024
Stanford University
2009-2019
Howard Hughes Medical Institute
2015-2019
Specific proteins are concentrated within primary cilia, whereas others remain excluded. To understand the mechanistic basis of entry into we developed an in vitro assay using cells which plasma membrane was permeabilized, but ciliary left intact. Using a diffusion-to-capture system and quantitative analysis, find that >9 nm diameter (∼100 kD) restricted from entering confirm these findings vivo. Interference with nuclear pore complex (NPC) or actin cytoskeleton permeabilized demonstrated...
The dynamic organization of signaling cascades inside primary cilia is key to signal propagation. Yet little known about the dynamics ciliary membrane proteins besides a possible role for motor-driven Intraflagellar Transport (IFT). To characterize these dynamics, we imaged single molecules Somatostatin Receptor 3 (SSTR3, GPCR) and Smoothened (Smo, Hedgehog transducer) in membrane. While IFT trains moved processively from one end cilium other, SSTR3 Smo underwent mostly diffusive behavior...
Pop goes the coccus Daughter cell separation in Staphylococcus aureus proceeds much like cracking of an egg. So say Zhou et al. , who examined dividing cells with millisecond precision using high-speed videomicroscopy. Rather than proceeding gradually, tiny imperfections mother wall were seen to crack open, leaving two daughter linked by a hinge. Science this issue p. 574
Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, their effects on Pol nucleosome crossing dynamics, is still missing. Here, we obtain topographic transcriptional residence time) maps canonical, H2A.Z, monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution accuracy. dynamics are complex, displaying pauses...
Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network constitutes a system for delivering luminal solutes, including Ca2+, across the cell periphery. How ER structure enables this nanofluidic is unclear. Here, we show that membrane-localized reticulon 4 (RTN4/Nogo) sufficient to impose neurite outgrowth inhibition in human cortical neurons while acting as an morphoregulator....
The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to perturbations, which have been implicated in several neuronal pathologies. One key functions enabling Ca <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:msup> <mml:mrow/> <mml:mrow> <mml:mn>2</mml:mn>...
Listeria monocytogenes hijacks host actin to promote its intracellular motility and intercellular spread. While L. virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy statistical modeling demonstrate that proceeds anisotropically an epithelial monolayer culture. We show boundaries infection foci are irregular dominated by rare pioneer bacteria farther than rest. extend our...
Neuronal morphology influences synaptic connectivity and neuronal signal processing. However, it remains unclear how shape affects steady-state distributions of organelles like mitochondria. In this work, we investigated the link between mitochondrial transport dendrite branching patterns by combining mathematical modeling with in vivo measurements architecture, motility, localization Drosophila HS (horizontal system) neurons. our model, different forms morphological scaling rules—which set...
We construct an efficient methodology for calculating wormlike chain statistics in arbitrary D dimensions over all rigidities, from fully rigid to completely flexible. The structure of our exact analytical solution the end-to-end distribution function a Fourier-Laplace space (i.e., Fourier-transformed end position and Laplace-transformed length) adopts form infinite continued fraction, which is advantageous its compact stability numerical implementation. then proceed present step-by-step...
Studying the statistical and dynamic behavior of semiflexible polymers under complex conditions generally requires discretizing polymer into a sequence beads for purposes simulation. We present novel approach generating coarse-grained, discretized models designed to reproduce statistics at intermediate long lengths. Our versatile model allows an arbitrary discretization length is accurate over larger range scales than traditional bead–rod bead–spring models. In its generality, discrete,...
Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs timescales shorter than the neuronal lifespan, necessitating transport of fresh material from soma. Maintaining an optimal distribution healthy requires interplay between a stationary pool sites high demand and motile capable delivering new material. Interchange these pools can occur via transient fusion / fission events or by halting restarting entire mitochondria. Our...
Autophagosome-lysosome fusion is required to clear cellular waste and maintain neuronal homeostasis. Computational modeling microscopy elucidate the dynamics of autophagosome-lysosome interaction in axons. Each autophagosome fuses with only a few lysosomes, autophagosomal maturation limited by slow kinetics inner membrane breakdown.
The endoplasmic reticulum (ER) is a dynamic network of interconnected sheets and tubules that orchestrates the distribution lipids, ions, proteins throughout cell. impact its complex, morphology on function as an intracellular transport hub remains poorly understood. To elucidate functional consequences ER structure dynamics, we quantify how heterogeneity peripheral in COS7 cells affects diffusive protein transport. In vivo imaging photoactivated membrane demonstrates their nonuniform...
In many cell types, mitochondria undergo extensive fusion and fission to form dynamic, responsive network structures that contribute a number of homeostatic, metabolic, signaling functions. The relationship between the dynamic interactions individual mitochondrial units cell-scale architecture remains an open area study. this work, we use coarse-grained simulations approximate analytic models establish how morphology is governed by local mechanical kinetic parameters. transition fragmented...
While a variety of double-ended transition state search methods have been developed, their relative performance in characterizing complex multistep pathways between structurally disparate molecular conformations remains unclear. Three such (doubly-nudged elastic band, string method, and growing method) are compared for series benchmarks ranging from permutational isomerizations the seven-atom Lennard-Jones cluster (LJ(7)) to highly cooperative LJ(38) LJ(75) rearrangements, folding two...
We analyze the response of a single nucleosome to tension, which serves as prototypical biophysical measurement where tension-dependent deformation alters transition kinetics. develop statistical-mechanics model wormlike chain bound spool, incorporating fluctuations in number bases bound, spool orientation, and conformations unbound polymer segments. With resulting free-energy surface, we perform dynamic simulations that permit direct comparison with experiments. This simple approach...
Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In rat axons, mitochondria respond glucose levels halting active transport high regions. We employ quantitative modeling explore physical limits on spatial organization of localized enhancement through regulated stopping processive motion. delineate the role key parameters, including cellular uptake consumption rates, that are expected mitochondrial...
The function of many membrane-enclosed intracellular structures relies on release diffusing particles that exit through narrow pores or channels in the membrane. rate varies with pore size, density, and length channel. We propose a simple approximate model, validated stochastic simulations, for estimating effective from cylinders, other simple-shaped domains, as channel parameters. results demonstrate that, very small pores, low density scattered over boundary is sufficient to achieve...