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A molecular imaging biosensor detects in vivo protein folding and misfolding

Overview of attention for article published in Journal of Molecular Medicine, June 2016
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Title
A molecular imaging biosensor detects in vivo protein folding and misfolding
Published in
Journal of Molecular Medicine, June 2016
DOI 10.1007/s00109-016-1437-9
Pubmed ID
Authors

Anjali V. Sheahan, Thillai V. Sekar, Kai Chen, Ramasamy Paulmurugan, Tarik F. Massoud

Abstract

Aberrant protein folding represents the molecular basis of many important human diseases. Although the discovery of new anti-misfolding drugs is a major priority in molecular therapeutics, there is currently no generalizable protein folding assay for use in cell-based high throughput screening (HTS) of chemical libraries, or for in vivo imaging. We molecularly engineered a bioluminescence-based biosensor composed of rationally split Firefly luciferase reporter fragments flanking a test protein, and used this in a protein-fragment complementation assay to quantitatively measure folding of the test protein. We comprehensively validated this biosensor in vitro, in cells, and by optically imaging protein folding and misfolding in living mice using several test proteins including enhanced green fluorescent protein, Renilla luciferase, Gaussia luciferase, and SIRT1. Applications of this novel biosensor are potentially far-reaching in both cell-based HTS approaches to discover new anti-misfolding drugs, and when using the same biosensor in validation studies of drug candidates in small animal models. Novel anti-misfolding drugs are needed as molecular therapeutics for many diseases. We developed first in vivo imaging protein folding biosensor to aid drug discovery. Biosensor created by flanking a test protein with rationally split Firefly luciferase. Biosensor validated by detecting folding of test proteins EGFP, Rluc, Gluc, and SIRT1. Generalizable molecular biosensor for translational applications in drug screening.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Israel 1 7%
Unknown 13 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 36%
Student > Master 3 21%
Other 2 14%
Researcher 2 14%
Professor 1 7%
Other 0 0%
Unknown 1 7%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 29%
Pharmacology, Toxicology and Pharmaceutical Science 2 14%
Chemistry 2 14%
Engineering 2 14%
Agricultural and Biological Sciences 1 7%
Other 0 0%
Unknown 3 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 June 2016.
All research outputs
#10,832,703
of 12,219,487 outputs
Outputs from Journal of Molecular Medicine
#934
of 1,073 outputs
Outputs of similar age
#229,424
of 276,950 outputs
Outputs of similar age from Journal of Molecular Medicine
#20
of 31 outputs
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So far Altmetric has tracked 1,073 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.