ArticleCell2020
Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning.
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Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses that pooled it.
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109citing papers in PubMed, 2 pooled it
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Who cites it
109 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Integrating AI with Biosensors and Voltammetry for Neurotransmitter Detection and Quantification: A Systematic Review.Biosensors · 2025Pooled it
- Meta-analysis of high-intensity interval training effects on cognitive function in older adults and cognitively impaired patients.Frontiers in physiology · 2025Pooled it
- Serotonin biology as a basis for explaining psychedelic drug action.Current biology : CB · 2026Review
- Illuminating spatial dynamics of glutamine metabolism with a sensitive genetically encoded biosensor.RSC chemical biology · 2026Article
- Noninvasive methods to monitor dynamic single-cell events.Trends in cell biology · 2026Review
- Protein Surface Site Determines the Evolutionary Accessibility of Allosteric Regulation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Fast analysis and engineering of protein function by microbe-independent deep assembly and screening.Molecular systems biology · 2026Article
- In vivo multimodal neurochemical interfaces for real-time decoding of brain circuit.Nature reviews. Neuroscience · 2026Review
- Machine Learning for Neurotransmitter Monitoring by Fast Voltammetry: Current and Future Prospects.ACS chemical neuroscience · 2026Review
- Causal links between serotonin dynamics and cued fear learning: evidence from experimental studies.Frontiers in computational neuroscience · 2026Review
- Article
- A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics.Nature communications · 2025Article
- Progress toward Multianalyte Neurochemical Detection: Techniques and Applications.ACS chemical neuroscience · 2025Review
- An Improved Ratiometric FRET Biosensor with Higher Affinity for Extracellular ATP.Sensors (Basel, Switzerland) · 2025Article
- Combing Directed Enzyme Evolution with Metabolic Engineering to Develop Efficient Microbial Cell Factories.Chem & bio engineering · 2025Review
- Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Review
- Recent advances in spying on cell signaling with fluorescent biosensors.Current opinion in cell biology · 2025Review
- Coding principles and mechanisms of serotonergic transmission modes.Molecular psychiatry · 2025Article
- Multiplexing FSCV and iGluSnFR3 Sensors Reveals Adenosine Transiently Inhibits Stimulated Dopamine and Glutamate Release.Journal of neurochemistry · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors.
Elizabeth K UngerDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Jacob P KellerJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA.
Michael AltermattDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Ruqiang LiangDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Aya MatsuiLaboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Chunyang DongDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Olivia J HonBowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Zi YaoDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Junqing SunDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Samba BanalaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA.
Meghan E FlaniganBowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
David A JaffeDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Samantha HartantoDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Jane CarlenDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Grace O MizunoDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Phillip M BordenJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA.
Amol V ShivangeDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Lindsay P CameronDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Steffen SinningDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Suzanne M UnderhillLaboratory of Molecular and Cellular Neurobiology, National Institute on Mental Health, NIH, Bethesda, MD 20892, USA.
David E OlsonDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Susan G AmaraLaboratory of Molecular and Cellular Neurobiology, National Institute on Mental Health, NIH, Bethesda, MD 20892, USA.
Duncan Temple LangDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Gary RudnickDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
Jonathan S MarvinJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA.
Luke D LavisJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA.
Henry A LesterDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Veronica A AlvarezLaboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
Andrew J FisherDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Jennifer A PrescherDepartment of Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
Thomas L KashBowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Vladimir Yarov-YarovoyDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA.
Viviana GradinaruDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Loren L LoogerJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20174, USA. Electronic address: loogerl@hhmi.org.
Lin TianDepartments of Biochemistry and Molecular Medicine, Chemistry, Statistics, Molecular and Cellular Biology, and Physiology and Membrane Biology, the Center for Neuroscience, and Graduate Programs in Molecular, Cellular, and Integrative Physiology, Biochemistry, Molecular, Cellular and Developmental Biology and Neuroscience, University of California, Davis, Davis, CA 95616, USA. Electronic address: lintian@ucdavis.edu.
Funding
UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2003 to 2026
$46.3MUser Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2MSynaptic mechanisms underlying reward seeking and compulsive drug useZIAAA000421 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI ALVAREZ, VERONICA A · 2009 to 2025
$23.1MRESEARCH TRAINING IN THE NEUROSCIENCEST32NS007431 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Juan Song, Mark J. Zylka · 1997 to 2026
$10.0MThe Role of Serotonin in Alcohol-Withdrawal Induced AnxietyR01AA019454 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2010 to 2026
$5.6MFluorescent biosensors for subcellular pharmacokineticsR01GM123582 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2016 to 2021
$3.8MGenetically encoded indicators for large-scale sensing of neuromodulatory signaling in behaving animalsU01NS103522 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI NIMMERJAHN, AXEL, TIAN, LIN · 2017 to 2019
$2.9Mpurchase of an All-in-One Fluorescence MicroscopeR01GM107630 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PRESCHER, JENNIFER · 2013 to 2021
$2.6MLearning, Memory, and Plasticity (LaMP) Training ProgramT32MH112507 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Karen Zito · 2017 to 2026
$2.4MFluorescent biosensors for imaging neurotransmitters: observing synapses in actioDP2MH107056 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI TIAN, LIN · 2014 to 2014
$2.3MNoninvasive Gene Delivery for Monitoring and Perturbing Cell Types and Circuits in Transgenic and Non-Transgenic AnimalsRF1MH117069 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI GRADINARU, VIVIANA · 2018 to 2018
$2.3MNew tools for quantitative non-invasive recording of biochemical signalsR01CA279813 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jennifer Prescher, Nathan Christopher Shaner · 2024 to 2026
$2.0MHoward Hughes Medical InstituteIntramural NIH HHS ZIA AA000421NCI NIH HHS R01 CA279813NCRR NIH HHS S10 RR029205NIAAA NIH HHS P60 AA011605NIAAA NIH HHS R01 AA019454NIAAA NIH HHS U24 AA025475NIDA NIH HHS R01 DA034388NIGMS NIH HHS P30 GM124165NIGMS NIH HHS R01 GM107630NIGMS NIH HHS R01 GM123582NIMH NIH HHS DP2 MH107056NIMH NIH HHS RF1 MH117069NIMH NIH HHS T32 MH112507NINDS NIH HHS T32 NS007431NINDS NIH HHS U01 NS090604NINDS NIH HHS U01 NS103522
Abstract
Serotonin plays a central role in cognition and is the target of most pharmaceuticals for psychiatric disorders. Existing drugs have limited efficacy; creation of improved versions will require better understanding of serotonergic circuitry, which has been hampered by our inability to monitor serotonin release and transport with high spatial and temporal resolution. We developed and applied a binding-pocket redesign strategy, guided by machine learning, to create a high-performance, soluble, fluorescent serotonin sensor (iSeroSnFR), enabling optical detection of millisecond-scale serotonin transients. We demonstrate that iSeroSnFR can be used to detect serotonin release in freely behaving mice during fear conditioning, social interaction, and sleep/wake transitions. We also developed a robust assay of serotonin transporter function and modulation by drugs. We expect that both machine-learning-guided binding-pocket redesign and iSeroSnFR will have broad utility for the development of other sensors and in vitro and in vivo serotonin detection, respectively.
Indexed as
Directed Molecular EvolutionMachine LearningAlgorithmsAmino Acid SequenceAmygdalaAnimalsBehavior, AnimalBinding SitesBrainHEK293 CellsHumansKineticsLinear ModelsMiceMice, Inbred C57BLPhotonsSerotoninSerotonin Plasma Membrane Transport Proteinsfear-learningfiber photometryfluorescence protein sensoriSeroSnFRmachine learningOSTAserotoninSERTsleep-wakesocial behaviors
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.