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Publication details

Document type
Journal articles

Document subtype
Full paper

Title
Protein Traffic Disorders: an Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery

Participants in the publication
Hugo M. Botelho (Author)
BioISI - Biosystems & Integrative Sciences Institute
 Dep. Química e Bioquímica
 Inna Uliyakina (Author)
Nikhil T. Awatade (Author)
Maria C. Proença (Author)
Dep. Física
 Christian Tischer (Author)
Lalida Sirianant (Author)
Karl Kunzelmann (Author)
Rainer Pepperkok (Author)
Margarida D. Amaral (Author)
BioISI
Summary
Plasma membrane proteins are essential molecules in the cell which mediate interactions with the exterior milieu, thus representing key drug targets for present pharma. Not surprisingly, protein traffic disorders include a large range of diseases sharing the common mechanism of failure in the respective protein to reach the plasma membrane. However, specific therapies for these diseases are remarkably lacking. Herein, we report a robust platform for drug discovery applied to a paradigmatic genetic disorder affecting intracellular trafficking - Cystic Fibrosis. This platform includes (i) two original respiratory epithelial cellular models incorporating an inducible double-tagged traffic reporter; (ii) a plasma membrane protein traffic assay for high-throughput microscopy screening; and (iii) open-source image analysis software to quantify plasma membrane protein traffic. By allowing direct scoring of compounds rescuing the basic traffic defect, this platform enables an effective drug development pipeline, which can be promptly adapted to any traffic disorder-associated protein and leverage therapy development efforts.

Date of Submisson/Request
2015-01-16
Date of Acceptance
2015-02-13
Date of Publication
2015-03-12

Institution
BioISI - Biosystems & Integrative Sciences Institute

Where published
Scientific Reports

Publication Identifiers
ISSN - 2045-2322

Publisher
Springer Science and Business Media LLC

Volume
5
Number
1

Document Identifiers
DOI - https://doi.org/10.1038/srep09038
URL - http://dx.doi.org/10.1038/srep09038


Export

APA
Hugo M. Botelho, Inna Uliyakina, Nikhil T. Awatade, Maria C. Proença, Christian Tischer, Lalida Sirianant, Karl Kunzelmann, Rainer Pepperkok, Margarida D. Amaral, (2015). Protein Traffic Disorders: an Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery. Scientific Reports, 5, ISSN 2045-2322. eISSN . http://dx.doi.org/10.1038/srep09038

IEEE
Hugo M. Botelho, Inna Uliyakina, Nikhil T. Awatade, Maria C. Proença, Christian Tischer, Lalida Sirianant, Karl Kunzelmann, Rainer Pepperkok, Margarida D. Amaral, "Protein Traffic Disorders: an Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery" in Scientific Reports, vol. 5, 2015. 10.1038/srep09038

BIBTEX
@article{39282, author = {Hugo M. Botelho and Inna Uliyakina and Nikhil T. Awatade and Maria C. Proença and Christian Tischer and Lalida Sirianant and Karl Kunzelmann and Rainer Pepperkok and Margarida D. Amaral}, title = {Protein Traffic Disorders: an Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery}, journal = {Scientific Reports}, year = 2015, volume = 5 }