title: A designer cell-based histamine-specific human allergy profiler.
abstract: Allergic disorders are markedly increasing in industrialized countries. The identification of compounds that trigger the immunoglobulin E-dependent allergic reaction remains the key to limit patients' exposure to critical allergens and improve their quality of life. Here we use synthetic biology principles to design a mammalian cell-based allergy profiler that scores the allergen-triggered release of histamine from whole-blood-derived human basophils. A synthetic signalling cascade engineered within the allergy profiler rewires histamine input to the production of reporter protein, thereby integrating histamine levels in whole-blood samples with remarkable sensitivity and a wide dynamic range, allowing for rapid results or long-term storage of output, respectively. This approach provides non-intrusive allergy profiles for the personalized medicine era.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Ausländer
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Eggerschwiler
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Kemmer
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Geering
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Ausländer
authors.affiliation: 1] Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland [2] Faculty of Science, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D000485:Allergens / Q000737:chemistry; D000818:Animals; D001491:Basophils / Q000166:cytology / Q000378:metabolism; D016466:CHO Cells; D003412:Cricetulus; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006632:Histamine / Q000737:chemistry*; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D011058:Pollen / Q000737:chemistry; D057285:Precision Medicine / Q000379:methods*; D011788:Quality of Life; D058615:Synthetic Biology; D019076:Transgenes
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D006632:Histamine
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