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Related Concept Videos

Protein Dynamics in Living Cells01:19

Protein Dynamics in Living Cells

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Different fluorescence-based techniques are used to study the protein dynamics in living cells. These techniques include FRAP, FRET, and PET.
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...
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High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
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Deciphering Drug Targets and Actions with Single-Cell and Spatial Resolution.

Zhengyuan Pang1, Benjamin F Cravatt2, Li Ye1,3

  • 1Department of Neuroscience, The Scripps Research Institute, La Jolla, California, USA;

Annual Review of Pharmacology and Toxicology
|September 18, 2023
PubMed
Summary
This summary is machine-generated.

New methods link drug-target interactions with cellular and spatial tissue heterogeneity. Integrating single-cell and spatial omics with drug imaging will advance understanding of in vivo drug mechanisms.

Keywords:
CATCHchemoproteomicsdrug-target interactionsmechanism of actionsingle cellspatial omics

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Area of Science:

  • Chemical biology
  • Genomics
  • Molecular biology
  • Biotechnology

Background:

  • Advances in chemical, molecular, and genetic methods enable whole-proteome and genome drug-target interaction identification.
  • Single-cell and spatial omics technologies are transforming the understanding of biological systems' molecular architecture.
  • A gap exists in aligning traditional drug action understanding (molecular affinities) with in vivo cellular and spatial tissue heterogeneity.

Purpose of the Study:

  • To review state-of-the-art methods for profiling drug-target interactions.
  • To discuss emerging multiomics tools for delineating tissue heterogeneity at single-cell resolution.
  • To highlight advances in in situ small-molecule drug imaging.

Main Methods:

  • Review of current drug-target interaction profiling techniques.
  • Exploration of single-cell and spatial omics for tissue heterogeneity analysis.
  • Focus on clearing-assisted tissue click chemistry (CATCH) for multiplexable in situ drug imaging.

Main Results:

  • Identification of methods to profile drug-target interactions across proteome and genome.
  • Characterization of tissue heterogeneity using single-cell and spatial omics.
  • Demonstration of high-resolution, multiplexable in situ small-molecule drug imaging via CATCH.

Conclusions:

  • Integration of single-cell and spatial omics platforms is crucial for future drug discovery.
  • Bridging the gap between molecular affinities and in vivo heterogeneity is key to understanding drug mechanisms.
  • The future framework for defining in vivo drug-target interactions will incorporate multiomics data and advanced imaging techniques.