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Directed Evolution of Protein-Based Neurotransmitter Sensors for MRI

Romero, Philip A. and Shapiro, Mikhail G. and Arnold, Frances H. and Jasanoff, Alan (2013) Directed Evolution of Protein-Based Neurotransmitter Sensors for MRI. In: Chemical Neurobiology : Methods and Protocols. Methods in Molecular Biology. No.995. Springer , New York, NY, pp. 193-205. ISBN 978-1-62703-344-2. PMCID PMC3818115.

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The production of contrast agents sensitive to neuronal signaling events is a rate-limiting step in the development of molecular-level functional magnetic resonance imaging (molecular fMRI) approaches for studying the brain. High-throughput generation and evaluation of potential probes are possible using techniques for macromolecular engineering of protein-based contrast agents. In an initial exploration of this strategy, we used the method of directed evolution to identify mutants of a bacterial heme protein that allowed detection of the neurotransmitter dopamine in vitro and in living animals. The directed evolution method involves successive cycles of mutagenesis and screening that could be generalized to produce contrast agents sensitive to a variety of molecular targets in the nervous system.

Item Type:Book Section
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URLURL TypeDescription CentralArticle
Romero, Philip A.0000-0002-2586-7263
Shapiro, Mikhail G.0000-0002-0291-4215
Arnold, Frances H.0000-0002-4027-364X
Jasanoff, Alan0000-0002-2834-6359
Additional Information:© 2013 Springer Science+Business Media New York. We are grateful to Robert Langer and to collaborators in the Arnold and Jasanoff laboratories for participation in the initial research and discussions that helped establish this protocol. We thank Eric Brustad for preliminary data used in some of the figures. MGS acknowledges the Fannie and John Hertz Foundation and the Paul and Daisy Soros Fellowship for support. This work was funded by NIH grant numbers R01-DA28299 and DP2-OD2441 (New Innovator Award) to A.J., and NIH grant number R01-GM068664 and a grant from the Caltech Jacobs Institute for Molecular Medicine to F.H.A.
Funding AgencyGrant Number
Fannie and John Hertz FoundationUNSPECIFIED
Paul and Daisy Soros FellowshipUNSPECIFIED
Caltech Jacobs Institute for Molecular MedicineUNSPECIFIED
Subject Keywords:Magnetic resonance imaging, Directed evolution, Protein engineering, Cytochrome P450, Dopamine
Series Name:Methods in Molecular Biology
Issue or Number:995
PubMed Central ID:PMC3818115
Record Number:CaltechAUTHORS:20130410-132453635
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:37862
Deposited By: Ruth Sustaita
Deposited On:10 Apr 2013 20:56
Last Modified:09 Nov 2021 23:31

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