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Chemogenetic fingerprinting by analysis of cellular growth dynamics

Warringer, Jonas; Anevski, Dragi LU ; Liu, Beidong and Blomberg, Anders (2008) In BMC Chemical Biology 8(3).
Abstract
Background: A fundamental goal in chemical biology is the elucidation of on- and off-target effects of drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes in cellular fitness, typically taken as changes in composite growth, is commonly applied.

Results: Using the model organism Saccharomyces cerevisiae we here report that resolving cellular growth dynamics into its individual components, growth lag, growth rate and growth efficiency, increases the predictive power of chemogenetic screens. Both in terms of drug-drug and gene-drug interactions did the individual growth variables capture distinct and only partially overlapping aspects of cell physiology. In fact, the impact on cellular growth... (More)
Background: A fundamental goal in chemical biology is the elucidation of on- and off-target effects of drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes in cellular fitness, typically taken as changes in composite growth, is commonly applied.

Results: Using the model organism Saccharomyces cerevisiae we here report that resolving cellular growth dynamics into its individual components, growth lag, growth rate and growth efficiency, increases the predictive power of chemogenetic screens. Both in terms of drug-drug and gene-drug interactions did the individual growth variables capture distinct and only partially overlapping aspects of cell physiology. In fact, the impact on cellular growth dynamics represented functionally distinct chemical fingerprints.

Discussion: Our findings suggest that the resolution and quantification of all facets of growth increases the informational and interpretational output of chemogenetic screening. Hence, by facilitating a physiologically more complete analysis of gene-drug and drug-drug interactions the here reported results may simplify the assignment of mode-of-action to orphan bioactive compounds. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Chemical Biology
volume
8
issue
3
publisher
BioMed Central
external identifiers
  • scopus:51349167425
ISSN
1472-6769
DOI
10.1186/1472-6769-8-3
language
English
LU publication?
no
id
755b07b5-fe9b-40e5-afc2-1b1684c349c6 (old id 1494795)
date added to LUP
2009-10-23 12:57:48
date last changed
2017-08-13 03:55:55
@article{755b07b5-fe9b-40e5-afc2-1b1684c349c6,
  abstract     = {Background: A fundamental goal in chemical biology is the elucidation of on- and off-target effects of drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes in cellular fitness, typically taken as changes in composite growth, is commonly applied.<br/><br>
Results: Using the model organism Saccharomyces cerevisiae we here report that resolving cellular growth dynamics into its individual components, growth lag, growth rate and growth efficiency, increases the predictive power of chemogenetic screens. Both in terms of drug-drug and gene-drug interactions did the individual growth variables capture distinct and only partially overlapping aspects of cell physiology. In fact, the impact on cellular growth dynamics represented functionally distinct chemical fingerprints.<br/><br>
Discussion: Our findings suggest that the resolution and quantification of all facets of growth increases the informational and interpretational output of chemogenetic screening. Hence, by facilitating a physiologically more complete analysis of gene-drug and drug-drug interactions the here reported results may simplify the assignment of mode-of-action to orphan bioactive compounds.},
  author       = {Warringer, Jonas and Anevski, Dragi and Liu, Beidong and Blomberg, Anders},
  issn         = {1472-6769},
  language     = {eng},
  number       = {3},
  publisher    = {BioMed Central},
  series       = {BMC Chemical Biology},
  title        = {Chemogenetic fingerprinting by analysis of cellular growth dynamics},
  url          = {http://dx.doi.org/10.1186/1472-6769-8-3},
  volume       = {8},
  year         = {2008},
}