A """"""""caged"""""""" molecule is a photosensitive, but temporarily inert, precursor of a biologically active molecule. Absorption of light transforms the precursor into a molecule with full bioactivity. Because light can be easily focused and steered, and photochemical changes are fast, caged molecules represent a versatile tool for manipulating biology with light with high temporal and spatial control. The long-term objective of this project is to develop a broad spectrum of caged molecules that will allow cellular physiologists to use light to probe and control dynamic signaling processes in living cells and tissues. This proposal has four foci: 1) Develop new """"""""cages"""""""" that have a) strong light absorption in single- and two-photon applications, b) high yield of product molecules upon photolysis, c) fast kinetics of product photorelease, and d) high pre-photolysis stability. 2) Develop new caged probes of neural signaling including neurotransmitters, lipid mediators, and inhibitors of transmitter transport. 3) Develop two new specific probes of intracellular calcium signaling: an optimal caged calcium and a caged agonist for the ryanodine receptor. 4) Apply the newly developed tools in ongoing and emerging independent and collaborative research to explore four topics in cellular neurophysiology: dendritic signal processing, synaptic plasticity, shaping of the synaptic event by glia, and calcium regulation of excitability.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM056481-06S1
Application #
6797093
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Shapiro, Bert I
Project Start
1998-04-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
6
Fiscal Year
2003
Total Cost
$63,960
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
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
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:
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

Showing the most recent 10 out of 50 publications