Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-16
pubmed:abstractText
We studied the distribution of expression levels amongst the cells of an Escherichia coli population carrying a gene-switching network, known as the genetic toggle. We employed two green fluorescent protein (GFP) reporter proteins with different half-lives and characterized the effect of isopropyl-beta-D-thiogalactopyranoside (IPTG) inducer concentration on fluorescence distribution characteristics. Our flow cytometric measurements indicated that there is a spread of fluorescence phenotypes of one to three orders of magnitude, due to the highly heterogeneous nature of the cell populations under investigation. Moreover, the shape of the distribution at a specific quasi-time-invariant reference state, defined for comparison purposes, strongly depended on inducer concentration. For very low and very high inducer concentrations, the distributions at the reference state are unimodal. On the contrary, for intermediate IPTG concentrations, two distinct subpopulations were formed below and above a single-cell threshold, resulting in distributions with a bimodal shape. The region of inducer concentrations where bimodality is observed is the same and independent of GFP half-life. Bimodal number density functions are not only obtained at the reference state. Transient studies revealed that even in cases where the distribution at the reference state is unimodal, the distribution becomes bimodal for a period of time required for the population to pass through the single-cell induction threshold. However, this feature was only captured by the system with the reduced half-life GFP. A simple single-cell model was used to shed light into the effect of inducer concentration and GFP half-life on the shape of the experimentally measured number density functions. The wide range of fluorescent phenotypes and the inability of the average population properties to fully characterize network behavior, indicate the importance of taking into account cell population heterogeneity when designing such a gene-switching network for biotechnological and biomedical applications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0168-1656
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
362-75
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cell population heterogeneity in expression of a gene-switching network with fluorescent markers of different half-lives.
pubmed:affiliation
Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77251-1892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural