Pathogen receptor discovery with a microfluidic human membrane protein array

Yair Glick; Ya'ara Ben-Ari; Nir Drayman; Michal Pellach; Gregory Neveu; Jim Boonyaratanakornkit; Dorit Avrahami; Shirit Einav; Ariella Oppenheim; Doron Gerber

doi:10.1073/pnas.1518698113

Pathogen receptor discovery with a microfluidic human membrane protein array

Yair Glick, Ya'ara Ben-Ari, Nir Drayman, Michal Pellach, Gregory Neveu, Jim Boonyaratanakornkit, Dorit Avrahami, Shirit Einav, Ariella Oppenheim, Doron Gerber

The Mina and Everard Goodman Faculty of Life Sciences - at Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The discovery of how a pathogen invades a cell requires one to determine which host cell receptors are exploited. This determination is a challenging problem because the receptor is invariably a membrane protein, which represents an Achilles heel in proteomics. We have developed a universal platform for high-throughput expression and interaction studies ofmembrane proteins by creating a microfluidic-based comprehensive human membrane protein array (MPA). The MPA is, to our knowledge, the first of its kind and offers a powerful alternative to conventional proteomics by enabling the simultaneous study of 2,100 membrane proteins. We characterized direct interactions of a whole nonenveloped virus (simian virus 40), as well as those of the hepatitis delta enveloped virus large form antigen, with candidate host receptors expressed on the MPA. Selected newly discovered membrane protein-pathogen interactions were validated by conventional methods, demonstrating that the MPA is an important tool for cellular receptor discovery and for understanding pathogen tropism.

Original language	English
Pages (from-to)	4344-4349
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	16
DOIs	https://doi.org/10.1073/pnas.1518698113
State	Published - 19 Apr 2016

Bibliographical note

Funding Information:
This work was supported by European Research Council Starter Grant 309600 (to D.G.); Israel Science Foundation Grant 715/11 (to D.G.) and Israel Science Foundation Grant 291/12 (to A.O.); American Cancer Society Grant RSG-14-11 0-0 1-MPC (to S.E.); Doris Duke Charitable Foundation Grant 2013100 (to S.E.). G.N. was supported by Child Health Research Institute, Lucile Packard Foundation for Children's Health, and Stanford Clinical and Translational Science Award Grant UL1 TR000093.

Funding

This work was supported by European Research Council Starter Grant 309600 (to D.G.); Israel Science Foundation Grant 715/11 (to D.G.) and Israel Science Foundation Grant 291/12 (to A.O.); American Cancer Society Grant RSG-14-11 0-0 1-MPC (to S.E.); Doris Duke Charitable Foundation Grant 2013100 (to S.E.). G.N. was supported by Child Health Research Institute, Lucile Packard Foundation for Children's Health, and Stanford Clinical and Translational Science Award Grant UL1 TR000093.

Funders	Funder number
American Cancer Society	RSG-14-11 0-0 1-MPC
Doris Duke Charitable Foundation
National Center for Advancing Translational Sciences	UL1TR001085
European Commission	309600
Israel Science Foundation	715/11, 291/12

Keywords

Integrated microfluidics
Membrane protein array
Pathogen-host interactions
Receptor discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1518698113

Cite this

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abstract = "The discovery of how a pathogen invades a cell requires one to determine which host cell receptors are exploited. This determination is a challenging problem because the receptor is invariably a membrane protein, which represents an Achilles heel in proteomics. We have developed a universal platform for high-throughput expression and interaction studies ofmembrane proteins by creating a microfluidic-based comprehensive human membrane protein array (MPA). The MPA is, to our knowledge, the first of its kind and offers a powerful alternative to conventional proteomics by enabling the simultaneous study of 2,100 membrane proteins. We characterized direct interactions of a whole nonenveloped virus (simian virus 40), as well as those of the hepatitis delta enveloped virus large form antigen, with candidate host receptors expressed on the MPA. Selected newly discovered membrane protein-pathogen interactions were validated by conventional methods, demonstrating that the MPA is an important tool for cellular receptor discovery and for understanding pathogen tropism.",

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Pathogen receptor discovery with a microfluidic human membrane protein array

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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