- Advanced Fluorescence Microscopy Techniques
- Nanoplatforms for cancer theranostics
- Click Chemistry and Applications
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Single-cell and spatial transcriptomics
- Neuroscience and Neuropharmacology Research
- Photochromic and Fluorescence Chemistry
- Dye analysis and toxicity
- Enzyme Catalysis and Immobilization
- RNA modifications and cancer
- Luminescence and Fluorescent Materials
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Neuroscience and Neural Engineering
- Electrochemical Analysis and Applications
- RNA Research and Splicing
- Photodynamic Therapy Research Studies
- Molecular Sensors and Ion Detection
- Advanced Chemical Sensor Technologies
- Advanced biosensing and bioanalysis techniques
- Gut microbiota and health
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Advanced Biosensing Techniques and Applications
University of California, Irvine
2022-2025
Janelia Research Campus
2019-2023
Howard Hughes Medical Institute
2019-2023
Helix (United States)
2019-2021
Rhodamine dyes exist in equilibrium between a fluorescent zwitterion and nonfluorescent lactone. Tuning this toward the lactone form can improve cell-permeability allow creation of "fluorogenic" compounds-ligands that shift to upon binding biomolecular target. An archetype fluorogenic dye is far-red tetramethyl-Si-rhodamine (SiR), which has been used create exceptionally useful labels for advanced microscopy. Here, we develop quantitative framework development new dyes, determining...
Fluorescence microscopy relies on dyes that absorb and then emit photons. In addition to fluorescence, fluorophores can undergo photochemical processes decrease quantum yield or result in spectral shifts irreversible photobleaching. Chemical strategies suppress these undesirable pathways—thereby increasing the brightness photostability of fluorophores—are crucial for advancing frontier bioimaging. Here, we describe a general method improve small-molecule by incorporating deuterium into...
The architecture of cells and the tissue they form within multicellular organisms are highly complex dynamic. Cells optimize their function microenvironments by expressing specific subsets RNAs. Advances in cell tagging methods enable spatial understanding RNA expression when merged with transcriptomics. However, these techniques currently limited resolution tagging, number RNAs that can be sequenced, multiplexing to isolate spatially-distinct same landscape. To address limitations, we...
Abstract Functional imaging using fluorescent indicators has revolutionized biology but additional sensor scaffolds are needed to access properties such as bright, far-red emission. We introduce a new platform for ‘chemigenetic’ indicators, utilizing the self-labeling HaloTag protein conjugated environmentally sensitive synthetic fluorophores. This approach affords calcium and voltage sensors with highly tunable photophysical chemical properties, which can reliably detect single action...
Abstract The ability to optically image cellular transmembrane voltage at millisecond-timescale resolution can offer unprecedented insight into the function of living brains in behaving animals. chemigenetic indicator Voltron is bright and photostable, making it a favorable choice for long vivo imaging neuronal populations resolution. Improving sensitivity would allow better detection spiking subthreshold signals. We performed site saturation mutagenesis 40 positions screened increased ΔF/F...
Abstract A core taken in a tree today can reveal climate events from centuries past. Here we adapt this idea to record histories of neural activation. We engineered slowly growing intracellular protein fibers which incorporate diverse fluorescent marks during growth store linear ticker tape-like histories. An embedded HaloTag reporter incorporated user-supplied HaloTag-ligand dyes, leading colored stripes whose boundaries mapped fiber wall-clock time. co-expressed eGFP tag driven by the cFos...
ABSTRACT Expanding the palette of fluorescent dyes is vital for pushing frontier biological imaging. Although rhodamine remain premier type small-molecule fluorophore due to their bioavailability and brightness, variants excited with far-red or near-infrared light suffer from poor performance propensity adopt a lipophilic, nonfluorescent form. We report general chemical modification rhodamines that optimizes long-wavelength enables facile functionalization different groups.
Herein, we detail a novel reverse-transcription (RT) assay to directly detect chemical adducts on RNA. We optimize fluorescence quenching RT polymerization and employ our approach N1-alkylation of inosine, an important post-transcriptional modification, using phenylacrylamide as model compound. anticipate can be expanded identify reagents that form with RNA further explored understand the relationship between processivity natural modifications in