Diarrheal diseases are one of the top ten causes of death in developing countries, with V. cholerae being one of the principal bacterial causative agents annually infecting an estimated ~4 million and killing ~120,000 people. Although an easily treatable disease, cholera continues to cause fatal epidemics because in practice clinical detection rarely occurs outside remote hospitals and environmental detection in water supplies remains challenging. The state-of-the- art for cholera diagnostics are purified antibodies used as dipstick tests; unfortunately dipstick tests are prohibitively expensive and unstable for use directly in local communities where cholera is endemic. A new transformative mode of detection will be needed to generate an extremely cheap and widely distributable system for continuous local surveillance of cholera. We sought to overcome current obstacles to local diagnostics by using existing synthetic biology components to craft a new class of cheap and simple diagnostic built around freeze-dried yeast. We avoid the need for expensive equipment and additional reagents by engineering yeast to produce the red tomato pigment lycopene in response to the cholera pathogen. We envision that engineered baker's yeast can be freeze-dried and then globally distributed to provide an inexpensive, safe, simple and reliable tool for monitoring of cholera in communities at risk for infection. If successful, this yeast platform will be easily redeployable for the detection of other pathogens.

Public Health Relevance

The objective of this proposal is to create a transformative technology for cholera detection using freeze-dried baker's yeast. This technology will provide an inexpensive, safe, simple and reliable tool for continuous monitoring of cholera and potentially other diseases in communities at risk for infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI110794-01A1
Application #
8886066
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Hall, Robert H
Project Start
2015-05-15
Project End
2020-04-30
Budget Start
2015-05-15
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Graduate Schools
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
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Ostrov, Nili; Jimenez, Miguel; Billerbeck, Sonja et al. (2017) A modular yeast biosensor for low-cost point-of-care pathogen detection. Sci Adv 3:e1603221
Anzalone, Andrew V; Lin, Annie J; Zairis, Sakellarios et al. (2016) Reprogramming eukaryotic translation with ligand-responsive synthetic RNA switches. Nat Methods 13:453-8