A5003904085- Advanced Fluorescence Microscopy Techniques
- Advanced Electron Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Advanced Biosensing Techniques and Applications
- Microfluidic and Bio-sensing Technologies
- Microtubule and mitosis dynamics
- Gene Regulatory Network Analysis
- Nonlinear Dynamics and Pattern Formation
- Genomics and Chromatin Dynamics
- Microfluidic and Capillary Electrophoresis Applications
- Image Processing Techniques and Applications
- Genetics, Bioinformatics, and Biomedical Research
- Photoacoustic and Ultrasonic Imaging
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Genetic and Kidney Cyst Diseases
- Photoreceptor and optogenetics research
- Immunotherapy and Immune Responses
- Fungal and yeast genetics research
- Nanoplatforms for cancer theranostics
- Advanced X-ray Imaging Techniques
- Single-cell and spatial transcriptomics
- Digital Holography and Microscopy
- Histone Deacetylase Inhibitors Research
- Genomics and Phylogenetic Studies
Rice University
2020-2025
The University of Texas MD Anderson Cancer Center
2023-2024
Institute of Bioengineering Technologies (United States)
2023
Stanford University
2016-2022
Karolinska Institutet
2017-2020
Palo Alto University
2020
University of Gothenburg
2012-2018
University of Hawaiʻi at Mānoa
2013
Tilted light sheet microscopy with 3D point spread functions (TILT3D) combines a novel, tilted illumination strategy long axial range (PSFs) for low-background, super-localization of single molecules as well super-resolution imaging in thick cells. Because the positions emitters are encoded shape each single-molecule image rather than position or thickness sheet, need not be extremely thin. TILT3D is built upon standard inverted microscope and has minimal custom parts. The result simple...
Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of mother centriole. These critical for formation primary cilium, by regulating at least four steps: ciliary vesicle recruitment, recruitment and initiation intraflagellar transport (IFT), removal CP110. While specific proteins that localize have been identified, how exactly each protein functions achieve multiple roles is poorly understood. Here we comprehensively analyze known newly discovered...
Single-molecule super-resolution imaging is instrumental in investigating cellular architecture and organization at the nanoscale. Achieving precise 3D nanometric localization when structures throughout mammalian cells, which can be multiple microns thick, requires careful selection of illumination scheme order to optimize fluorescence signal background ratio (SBR). Thus, an optical platform that combines different wide-field schemes for target-specific SBR optimization would facilitate more...
Protein intrinsically disordered regions (IDRs) are critical gene-regulatory components and aberrant fusions between IDRs DNA-binding/chromatin-associating domains cause diverse human cancers. Despite this importance, how influence gene expression, IDR fusion proteins provoke oncogenesis, remains incompletely understood. Here we develop a series of synthetic dCas9-IDR to establish that locus-specific recruitment can be sufficient stimulate endogenous expression. Using dCas9 fused the...
Yeast glycolytic oscillations have been studied since the 1950s in cell-free extracts and intact cells. For cells, sustained so far only observed at population level, i.e. for synchronized cultures high biomass concentrations. Using optical tweezers to position yeast cells a microfluidic chamber, we were able observe individual isolated detailed kinetic model cellular reactions, simulated heterogeneity response of assuming small differences single internal parameter. This is first time that...
Primary cilia in many cell types contain a periaxonemal subcompartment called the inversin compartment. Four proteins have been found to assemble within compartment: INVS, ANKS6, NEK8, and NPHP3. The function of compartment is unknown, but it appears be critical for normal development, including left-right asymmetry renal tissue homeostasis. Here we combine superresolution imaging human RPE1 cells, classic model studying primary vitro, with genetic dissection protein-protein binding...
Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of mother centriole. These critical for formation primary cilium, by regulating at least four steps: ciliary vesicle recruitment, recruitment and initiation intraflagellar transport (IFT), removal CP110. While specific proteins that localize have been identified, how exactly each protein functions achieve multiple roles is poorly understood. Here we comprehensively analyze known newly discovered...
Oscillations are widely distributed in nature and synchronization of oscillators has been described at the cellular level (e.g. heart cells) population fireflies). Yeast glycolysis is best known oscillatory system, although it studied almost exclusively (i.e. limited to observations average behaviour synchronized cultures). We individual yeast cells that were positioned with optical tweezers a microfluidic chamber determine precise conditions for autonomous glycolytic oscillations. Hopf...
We report the observation of chromatin dynamics in living budding yeast (Saccharomyces cerevisiae) cells, three-dimensions (3D). Using dual color localization microscopy and employing a Tetrapod point spread function, we analyze spatio-temporal two fluorescently labeled DNA loci surrounding GAL locus. From measured trajectories, obtain different dynamical characteristics terms inter-loci distance temporal variance; when locus is activated, 3D variance increase compared to inactive state....
Abstract Multi-target single-molecule super-resolution fluorescence microscopy offers a powerful means of understanding the distributions and interplay between multiple subcellular structures at nanoscale. However, imaging whole mammalian cells is often hampered by high background slow acquisition speeds, especially when targets in 3D. In this work, we have mitigated these issues developing steerable, dithered, single-objective tilted light sheet for optical sectioning to reduce pipeline 3D...
Single-molecule localization microscopy (SMLM) is a powerful tool for observing structures beyond the diffraction limit of light. Combining SMLM with engineered point spread functions (PSFs) enables 3D imaging over an extended axial range, as has been demonstrated super-resolution various cellular structures. However, super-resolving in thick samples, such whole mammalian cells, remains challenging it typically requires acquisition and postprocessing stitching multiple slices to cover entire...
Abstract Cell signaling, gene expression and metabolism are affected by cell-cell heterogeneity random changes in the environment. The effects of such fluctuations on cell signaling have recently been studied intensively using single-cell experiments. In may be particularly important because it affect synchronisation metabolic oscillations, an example communication. This is notoriously difficult to describe theoretically as glycolytic oscillations shows: neither mechanism understood nor role...
Chromatin organization and dynamics are critical for gene regulation. In this work we present a methodology fast parallel three-dimensional (3D) tracking of multiple chromosomal loci choice over many thousands frames on various timescales. We achieved by developing combining fluorogenic replenishable nanobody arrays, engineered point spread functions, light sheet illumination. The result is gentle live-cell 3D with excellent spatiotemporal resolution throughout the mammalian cell nucleus....
Centrosomes play a fundamental role in nucleating and organizing microtubules the cell are vital for faithful chromosome segregation maintenance of genomic stability. Loss structural or functional integrity centrosomes causes instability is driver oncogenesis. The lysine demethylase 4A (KDM4A) an epigenetic 'eraser' chromatin methyl marks, which we show also localizes to centrosome with single molecule resolution. We additionally discovered KDM4A enzymatic activity required maintain...