- Advanced Fluorescence Microscopy Techniques
- Bacteriophages and microbial interactions
- Orbital Angular Momentum in Optics
- DNA and Nucleic Acid Chemistry
- Microfluidic and Bio-sensing Technologies
- Force Microscopy Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- Mechanical and Optical Resonators
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Near-Field Optical Microscopy
- Evolution and Genetic Dynamics
- Cell Image Analysis Techniques
- Evolutionary Game Theory and Cooperation
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Advanced Biosensing Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- Photodynamic Therapy Research Studies
- Nanoplatforms for cancer theranostics
- Neural dynamics and brain function
- CAR-T cell therapy research
University of Toronto
2016-2025
University of Southern California
2023
University of Michigan
2010-2012
Michigan United
2011
California Institute of Technology
2007-2009
We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired a variety cerebral regions, show ubiquitous 1/f2 scaling within power spectrum. develop quantitative model treats generation these fields in an analogous way to electronic shot noise, and use this specifically address cause Brownian noise. The gives two analytically tractable solutions, both displaying noise: 1) uncorrelated cells display sharp initial activity,...
Single-molecule localization microscopy (SMLM) provides images of cellular structure at a resolution an order magnitude below what can be achieved by conventional diffraction limited techniques. The concomitantly larger data sets generated SMLM require increasingly efficient image analysis software. Density based clustering algorithms, with the most ubiquitous being DBSCAN, are commonly used to quantitatively assess sub-cellular assemblies. however, is slow, scaling number localizations like...
Antimicrobial photodynamic therapy (aPDT) utilizes light, oxygen and a photosensitizer (PS) to enact cell death via the production of reactive species (ROS). This mechanism death, oxidative stress, has allowed aPDT be effective against antibiotic-resistant bacterial strains, with development resistance being minimal as no specific pathway is targeted. While promising, ambient light can activate PSs, damage mammalian tissues occur, leading drug-induced photosensitivity. To mitigate this, we...
We show that minuscule entropic forces, on the order of 100 fN, can prevent formation DNA loops---a ubiquitous means regulating expression genes. observe a tenfold decrease in rate LacI-mediated loop when tension 200 fN is applied to substrate DNA, biasing thermal fluctuations drive and breakdown events. Conversely, once looped, DNA-protein complex insensitive force. Our measurements are excellent agreement with simple polymer model an antiparallel topology preferred LacI-DNA conformation...
Antibiotic resistance is a major problem for world health, triggered by the unnecessary usage of broad-spectrum antibiotics on purportedly infected patients. Current clinical standards require lengthy protocols detection bacterial species in sterile physiological fluids. In this work, class small-molecule fluorescent chemosensors termed ProxyPhos was shown to be capable rapid, sensitive, and facile bacteria. The sensors act via turn-on excimer mechanism, where close-proximity binding...
Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, is common means of regulating transcription, very much stochastic process; the loops arise from thermal motion and other fluctuations environment. We present single-molecule measurements loop formation breakdown when an artificial fluctuating force, applied to mimic environment, imposed on DNA. show that greatly enhanced presence noise only fraction ${k}_{B}T$,...
Multispecies bacterial populations often inhabit confined and densely packed environments where spatial competition determines the ecological diversity of community. However, role mechanical interactions in shaping ecology is still poorly understood. Here, we study a model system consisting two nonmotile Escherichia coli bacteria competing within open, monolayer microchannels. The competitive dynamics observed to be biphasic: After seeding, either one strain rapidly fixates or both strains...
Based on the membrane currents generated by an action potential in a biologically realistic model of pyramidal, hippocampal cell within rat CA1, we perform moment expansion extracellular field potential. We decompose into both inverse and classical moments show that this method is rapid efficient way to calculate near far from body. The gives rise large quadrupole contributes up distances almost 1 cm. This will serve as starting point connecting microscopic generation electric fields at...
Abstract Tethered particle motion (TPM) has become an important tool for single‐molecule studies of biomolecules; however, concerns remain that the method may alter dynamics biophysical process under study. We investigate effect attached microsphere on illustrative biological example: formation and breakdown protein‐mediated DNA loops in lac repressor system. By comparing data from a conventional TPM experiment with 800 nm polystyrene beads dark‐field using 50 Au nanoparticles, we found...
The bacterial chromosome is under varying levels of mechanical stress due to a high degree crowding and dynamic protein-DNA interactions experienced within the nucleoid. DNA tension difficult measure in cells its functional significance remains unclear although vitro experiments have implicated range biomechanical phenomena. Using single-molecule tools, we uncovered novel interaction that responds fluctuations by condensing DNA. We combined tethered particle motion (TPM) optical tweezers...
The heat-stable nucleoid-structuring (H-NS) protein is a global transcriptional regulator implicated in coordinating the expression of over 200 genes Escherichia coli, including many involved adaptation to osmotic stress. We have applied superresolved microscopy quantify intracellular and spatial reorganization H-NS response rapid shift. found that showed growth phase-dependent relocalization hyperosmotic shock. In stationary phase, detached from tightly compacted bacterial chromosome was...
Abstract Single‐molecule localization microscopy (SMLM) has the potential to revolutionize proteomic and genomic analyses by providing information on number stoichiometry of proteins or nucleic acids aggregating at spatial scales below diffraction limit light. Here, a method for molecular counting is presented with SMLM built upon exponentially distributed blinking statistics photoswitchable fluorophores, focus organic dyes. A guide performing this newly developed technique provided,...
Conventional optical tweezers suffer from several complications when applying axial forces to surface-tethered molecules. Aberrations the refractive-index mismatch between an oil-immersion objective's medium and aqueous trapping environment both shift trap centre degrade strength with focal depth. Furthermore, interference effects back-scattered light make it difficult use back-focal-plane interferometry for high-bandwidth position detection. Holographic were employed correct aberrations...
Studying the mechanical properties of short segments dsDNA can provide insight into various biophysical phenomena, from DNA looping to organization nucleosomes. Scanning atomic force microscopy (AFM) is able acquire images single molecules with near-basepair resolution. From many images, one may use equilibrium statistical mechanics quantify intrinsic stiffness (or persistence length) DNA. However, this approach highly dependent upon both correct microscopic polymer model and a image...
Background Allogeneic hematopoietic stem cell transplant remains the most effective strategy for patients with high-risk acute myeloid leukemia (AML). Leukemia-specific neoantigens presented by major histocompatibility complexes (MHCs) are recognized T receptors (TCR) triggering graft-versus-leukemia effect. A unique TCR signature is generated a complex V(D)J rearrangement process to form capable of binding peptide-MHC. The repertoire undergoes dynamic changes disease progression and...
Single-molecule localization microscopy (SMLM) is a powerful tool for studying intracellular structure and macromolecular organization at the nanoscale. The increasingly massive pointillistic data sets generated by SMLM require development of new highly efficient quantification tools. Here we present FOCAL3D, an accurate, flexible exceedingly fast (scaling linearly with number localizations) density-based algorithm quantifying spatial clustering in large 3D sets. Unlike DBSCAN, which perhaps...
Antimicrobial photodynamic therapy (APDT) employs a photosensitizer, light, and molecular oxygen to treat infectious diseases via oxidative damage, with low likelihood for the development of resistance. For optimal APDT efficacy, photosensitizers cationic charges that can permeate bacteria cells bind intracellular targets are desired not limit damage outer bacterial structure. Here we report application brominated DAPI (Br-DAPI), water-soluble, DNA-binding photosensitizer eradication both...
We have developed a correlation microscopy technique to follow the dynamics of quantum dot labeled DNA within living cells. The temporal functions labels reflect fluctuations nanoprobe as result its interactions with cellular environment. They provide sensitive measure for length probe on scale persistence (∼50 nm) and reveal strong nonthermal cell. These results pave way dynamic observations conformational changes in vivo.