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Proteomics

Proteomics

A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...

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Updated: Jun 18, 2026

Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions

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Published on: June 7, 2020

Cell Morphological Profiling Enables High-Throughput Screening for PROteolysis TArgeting Chimera (PROTAC) Phenotypic

Maria-Anna Trapotsi^1,2, Elizabeth Mouchet³, Guy Williams³

¹Department of Chemistry, Centre for Molecular Informatics, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.

ACS Chemical Biology

|July 6, 2022

Summary

PROteolysis TArgeting Chimeras (PROTACs) offer therapeutic benefits but require safety assessments. Cell Painting identified a novel mitotoxicity signature, improving PROTAC safety profiling and drug design.

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Area of Science:

Biochemistry
Pharmacology
Cell Biology

Background:

PROteolysis TArgeting Chimeras (PROTACs) are an emerging therapeutic modality utilizing the ubiquitin-proteasome system for targeted protein degradation.
Several PROTACs have advanced to clinical trials, highlighting the rapid progress in targeted protein degradation technology.

Purpose of the Study:

To establish robust methods for assessing the safety risks associated with PROTAC compounds.
To identify potential toxic liabilities early in the drug development process.

Main Methods:

Utilized Cell Painting, an unbiased high-content imaging technique, to detect phenotypic signatures induced by PROTACs.
Employed chemical clustering and predictive modeling to analyze the imaging data.

Main Results:

Identified a specific mitotoxicity signature associated with PROTACs, which was not apparent from analyzing individual components.
Demonstrated the efficacy of unbiased phenotypic screening in uncovering unexpected toxicological profiles.

Conclusions:

Unbiased phenotypic methods like Cell Painting are crucial for identifying safety risks of novel therapeutics such as PROTACs.
These findings can significantly impact and improve the design of safer and more efficacious PROTAC-based drugs.