In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-12-29)
Abstract:
Small molecules play essential roles in organisms, and so methods to sense these molecules within living cells could have wide-ranging uses in both biology and biotechnology. However, current methods for making new “biosensors” are limited and only a narrow range of small molecules can be detected. One approach to biosensor design in yeast and other eukaryotic organisms uses proteins called ligand-binding domains, which bind to small molecules. Here, Feng, Jester, Tinberg, Mandell et al. have developed a new method to make biosensors from ligand-binding domains that could, in principle, be applied to any target small molecule. The new method involves taking a ligand-binding domain that is either engineered or occurs in nature and linking it to something that can be readily detected, such as a protein that fluoresces or that controls gene expression. This combined biosensor protein is then engineered, via mutations, such that it is unstable unless it binds to the small molecule. This means that, in the absence of the small molecule, these proteins are destroyed inside living cells. However, the binding of a target molecule to one of these proteins protects it from degradation, which allows the signal to be detected. Feng, Jester, Tinberg, Mandell et al. use this method to create biosensors for a human hormone called progesterone and a drug called digoxin, which is used to treat heart disease. Further experiments used the biosensors to optimize the production of progesterone in yeast and to regulate the activity of a gene editing protein called Cas9 in human cells. The biosensors can be also used to produce long-term environmental sensors in plant cells. This approach makes it possible to produce a wide variety of biosensors for different organisms. The next step is to continue to explore the ability of various proteins to be converted into biosensors, and to find out how easy it is to transfer a biosensor produced in one species to another.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.10606.001
DOI:
10.7554/eLife.10606.002
DOI:
10.7554/eLife.10606.003
DOI:
10.7554/eLife.10606.004
DOI:
10.7554/eLife.10606.005
DOI:
10.7554/eLife.10606.006
DOI:
10.7554/eLife.10606.007
DOI:
10.7554/eLife.10606.008
DOI:
10.7554/eLife.10606.009
DOI:
10.7554/eLife.10606.010
DOI:
10.7554/eLife.10606.011
DOI:
10.7554/eLife.10606.012
DOI:
10.7554/eLife.10606.013
DOI:
10.7554/eLife.10606.014
DOI:
10.7554/eLife.10606.015
DOI:
10.7554/eLife.10606.016
DOI:
10.7554/eLife.10606.017
DOI:
10.7554/eLife.10606.018
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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