Abstract

The objective of this project is to develop a broad spectrum of optimized photosensitive probes (caged compounds) to allow cellular physiologists to use light to manipulate and control dynamic signaling processes in living cells. Specifically, the proposal has five major foci: 1) Develop new caging groups to achieve high product yield, high photorelease speed and high prephotolysis stability. 2) Synthesize caged probes for manipulating intracellular Ca2+ dynamics. Specific targets are a caged calcium and a caged anti-calcium optimized to address problems in cellular physiology, and a caged agonist for the ryanodine receptor. 3) Develop new caged neurotransmitters that are optimized for low prephotolysis agonist activity and very fast photorelease kinetics. 4) Develop a method for making caged peptides to allow photo-activation and photo- inhibition of intracellular enzyme activities. 5) Application of the newly created photochemical tools to four specific problems in three areas of cellular physiology; excitation-contraction coupling in cardiac cells, regulation of excitability in sensory neurons, and integration of synaptic inputs by neuronal dendrites.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056481-04
Application #
6386757
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Shapiro, Bert I
Project Start
1998-04-01
Project End
2002-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
4
Fiscal Year
2001
Total Cost
$230,735
Indirect Cost

  Institution

Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21202

  Publications

Deng, Rongkang; Kao, Joseph P Y; Kanold, Patrick O (2017) Distinct Translaminar Glutamatergic Circuits to GABAergic Interneurons in the Neonatal Auditory Cortex. Cell Rep 19:1141-1150
Meng, Xiangying; Kao, Joseph P Y; Lee, Hey-Kyoung et al. (2017) Intracortical Circuits in Thalamorecipient Layers of Auditory Cortex Refine after Visual Deprivation. eNeuro 4:
Meng, Xiangying; Winkowski, Daniel E; Kao, Joseph P Y et al. (2017) Sublaminar Subdivision of Mouse Auditory Cortex Layer 2/3 Based on Functional Translaminar Connections. J Neurosci 37:10200-10214
Nagode, Daniel A; Meng, Xiangying; Winkowski, Daniel E et al. (2017) Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder. Cell Rep 18:1100-1108
Weaver, John; Burks, Scott R; Liu, Ke Jian et al. (2016) In vivo EPR oximetry using an isotopically-substituted nitroxide: Potential for quantitative measurement of tissue oxygen. J Magn Reson 271:68-74
Legenzov, Eric A; Muralidharan, Sukumaran; Woodcock, Lukas B et al. (2016) Designing Molecular Probes To Prolong Intracellular Retention: Application to Nitroxide Spin Probes. Bioconjug Chem 27:2923-2930
Briggs, Katharine T; Giulian, Gary G; Li, Gong et al. (2016) A Molecular Model for Lithium's Bioactive Form. Biophys J 111:294-300
Meng, Xiangying; Kao, Joseph P Y; Lee, Hey-Kyoung et al. (2015) Visual Deprivation Causes Refinement of Intracortical Circuits in the Auditory Cortex. Cell Rep 12:955-64
Legenzov, Eric A; Sims, Stephen J; Dirda, Nathaniel D A et al. (2015) Disulfide-Linked Dinitroxides for Monitoring Cellular Thiol Redox Status through Electron Paramagnetic Resonance Spectroscopy. Biochemistry 54:6973-82
Burks, Scott R; Legenzov, Eric A; Martin, Erik W et al. (2015) Co-encapsulating the fusogenic peptide INF7 and molecular imaging probes in liposomes increases intracellular signal and probe retention. PLoS One 10:e0120982

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