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Directed Evolution of a Selective and Sensitive Serotonin Biosensor Via Machine Learning

87 Pages Posted: 9 Dec 2019 Publication Status: Published

See all articles by Elizabeth K. Unger

Elizabeth K. Unger

University of California, Davis - Department of Biochemistry and Molecular Medicine

Jacob Pearson Keller

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Michael Altermatt

California Institute of Technology - Division of Biology and Biological Engineering

Ruqiang Liang

University of California, Davis - Department of Biochemistry and Molecular Medicine

Zi Yao

University of California, Irvine - Department of Chemistry

Junqing Sun

University of California, Davis - Department of Pharmacology

Aya Matsui

National Institutes of Health (NIH) - Laboratory on Neurobiology of Compulsive Behaviors

Chunyang Dong

University of California, Davis - Department of Biochemistry and Molecular Medicine

David A. Jaffe

University of California, Davis - Department of Biochemistry and Molecular Medicine

Samantha Hartanto

University of California, Davis - Department of Biochemistry and Molecular Medicine

Grace Mizuno

University of California, Davis - Department of Biochemistry and Molecular Medicine

Phillip Borden

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Amol Shivange

California Institute of Technology - Division of Biology and Biological Engineering

Steffen Sinning

Yale University - Department of Pharmacology

Suzanne Underhill

National Institutes of Health - Laboratory of Molecular and Cellular Neurobiology

Jane Carlin

University of California, Davis - Department of Biochemistry and Molecular Medicine

Samba Banala

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Lindsay P. Cameron

University of California, Davis - Department of Biochemistry and Molecular Medicine

David E. Olson

University of California, Davis - Department of Biochemistry and Molecular Medicine

Susan Amara

National Institutes of Health - Laboratory of Molecular and Cellular Neurobiology

Duncan Temple Lang

University of California, Davis - Department of Biochemistry and Molecular Medicine

Gary Rudnick

Yale University - Department of Pharmacology

Jonathan Marvin

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Luke Lavis

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Henry A. Lester

California Institute of Technology - Division of Biology and Biological Engineering

Veronica Alvarez

National Institutes of Health (NIH) - Laboratory on Neurobiology of Compulsive Behaviors

Andrew J. Fisher

University of California, Davis - Department of Biochemistry and Molecular Medicine

Jennifer Prescher

University of California, Irvine - Department of Chemistry

Vladimir Yarov-Yarovoy

University of California, Davis - Department of Biochemistry and Molecular Medicine

Viviana Gradinaru

California Institute of Technology - Division of Biology and Biological Engineering

Loren Looger

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

Lin Tian

University of California, Davis - Department of Biochemistry and Molecular Medicine

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Abstract

Serotonin is involved in numerous critical physiologic and cognitive processes. Drugs that modulate serotonin transport are among the most widely used medications to treat pervasive mental disorders. Both a deeper understanding of serotoninergic circuitry and design of improved treatments will require the ability to measure serotonin release and transport with high spatial and temporal resolution. Here we developed and applied a binding-pocket redesign strategy guided by machine learning to create a high-performance soluble, fluorescent serotonin sensor (iSeroSnFR). This sensor has requisite selectivity and sensitivity needed for direct detection of serotonin transients in various biological systems, especially permits detection of subsecond-scale serotonin release events during fear conditioning and sleep-to-wakefulness transitions. Furthermore, the solubility of iSeroSnFR allowed us to develop a rapid, cytoplasmic sensor-based assay of serotonin transporter activity in the presence of pharmacological manipulations.

Suggested Citation

Unger, Elizabeth and Keller, Jacob Pearson and Altermatt, Michael and Liang, Ruqiang and Yao, Zi and Sun, Junqing and Matsui, Aya and Dong, Chunyang and Jaffe, David A. and Hartanto, Samantha and Mizuno, Grace and Borden, Phillip and Shivange, Amol and Sinning, Steffen and Underhill, Suzanne and Carlin, Jane and Banala, Samba and Cameron, Lindsay P. and Olson, David E. and Amara, Susan and Temple Lang, Duncan and Rudnick, Gary and Marvin, Jonathan and Lavis, Luke and Lester, Henry A. and Alvarez, Veronica and Fisher, Andrew J. and Prescher, Jennifer and Yarov-Yarovoy, Vladimir and Gradinaru, Viviana and Looger, Loren and Tian, Lin, Directed Evolution of a Selective and Sensitive Serotonin Biosensor Via Machine Learning (November 5, 2019). Available at SSRN: https://ssrn.com/abstract=3498571 or http://dx.doi.org/10.2139/ssrn.3498571
This version of the paper has not been formally peer reviewed.

Elizabeth Unger

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Jacob Pearson Keller

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus ( email )

19700 Helix Drive
Ashburn, VA 20147
United States

Michael Altermatt

California Institute of Technology - Division of Biology and Biological Engineering ( email )

Pasadena, CA 91125
United States

Ruqiang Liang

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Zi Yao

University of California, Irvine - Department of Chemistry

United States

Junqing Sun

University of California, Davis - Department of Pharmacology

One Shields Avenue
Davis, CA 95616
United States

Aya Matsui

National Institutes of Health (NIH) - Laboratory on Neurobiology of Compulsive Behaviors

United States

Chunyang Dong

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

David A. Jaffe

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Samantha Hartanto

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Grace Mizuno

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Phillip Borden

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

19700 Helix Drive
Ashburn, VA 20147
United States

Amol Shivange

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Steffen Sinning

Yale University - Department of Pharmacology

New Haven, CT 06520
United States

Suzanne Underhill

National Institutes of Health - Laboratory of Molecular and Cellular Neurobiology

United States

Jane Carlin

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Samba Banala

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

19700 Helix Drive
Ashburn, VA 20147
United States

Lindsay P. Cameron

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

David E. Olson

University of California, Davis - Department of Biochemistry and Molecular Medicine ( email )

One Shields Avenue
Davis, CA 95616
United States

Susan Amara

National Institutes of Health - Laboratory of Molecular and Cellular Neurobiology

United States

Duncan Temple Lang

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Gary Rudnick

Yale University - Department of Pharmacology

New Haven, CT 06520
United States

Jonathan Marvin

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

19700 Helix Drive
Ashburn, VA 20147
United States

Luke Lavis

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus

19700 Helix Drive
Ashburn, VA 20147
United States

Henry A. Lester

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Veronica Alvarez

National Institutes of Health (NIH) - Laboratory on Neurobiology of Compulsive Behaviors ( email )

United States

Andrew J. Fisher

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Jennifer Prescher

University of California, Irvine - Department of Chemistry

United States

Vladimir Yarov-Yarovoy

University of California, Davis - Department of Biochemistry and Molecular Medicine

One Shields Avenue
Davis, CA 95616
United States

Viviana Gradinaru

California Institute of Technology - Division of Biology and Biological Engineering ( email )

Pasadena, CA 91125
United States

Loren Looger

Howard Hughes Medical Institute (HHMI) - Chevy Chase - Janelia Research Campus ( email )

19700 Helix Drive
Ashburn, VA 20147
United States

Lin Tian (Contact Author)

University of California, Davis - Department of Biochemistry and Molecular Medicine ( email )

One Shields Avenue
Davis, CA 95616
United States

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