SPATIAL CONTROL OF INTRACELLULAR SIGNALING (Lee Bardwell, Theme Leader) | Some of the greatest mysteries in biological spafial dynamics lie at the subcellular level. The successes of biochemical and reconstitution-based assays in explaining fundamental mechanisms of cell biology have madeit easy to lose sight of the fact that cells are not just bags of well-sfirred enzymes. With respect to intracellular signaling pathways, there is growing evidence that spatial control is crucial to normal function [192-194] and occurs at many scales: compartments (plasma memtjrane, nucleus);sub-compartments (e.g. membrane rafts and nuclear speckles) and, below these levels, the nano-spafial scale, defined by local tethering interactions. Such spatial regulation is necessarily dynamic: scaffold proteins move to the plasma membrane, kinases and transcription factors move into or out of the nucleus, tethering interactions are regulated by phosphorylation, etc. In addifion, motor-based transport is used both to construct compartments, and to transport signaling molecules during sfimulafion;in turn this transport is regulated by extra- and intracellular cues. Yet for all the evidence that space matters, we often know less about spatial dynamics inside cells than outside of them. We propose three projects that deal with distinct,aspects of intracellular spatial dynamics, but are linked by their reliance on novel, cutting-edge optical, bioinformatic, and modeling methodologies. All three seek to open new lines of inquiry and, as such, incur more than a little technical risk. We believe the risks are justified by the expected gains in discovery and understanding in such a pooriy understood, yet extremely important, area.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
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Special Emphasis Panel (ZGM1-CBCB-3)
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University of California Irvine
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Malacrida, Leonel; Gratton, Enrico (2018) LAURDAN fluorescence and phasor plots reveal the effects of a H2O2 bolus in NIH-3T3 fibroblast membranes dynamics and hydration. Free Radic Biol Med 128:144-156
Malacrida, Leonel; Rao, Estella; Gratton, Enrico (2018) Comparison between iMSD and 2D-pCF analysis for molecular motion studies on in vivo cells: The case of the epidermal growth factor receptor. Methods 140-141:74-84
Hedde, Per Niklas; Gratton, Enrico (2018) Selective plane illumination microscopy with a light sheet of uniform thickness formed by an electrically tunable lens. Microsc Res Tech 81:924-928
Kobylkevich, Brian M; Sarkar, Anyesha; Carlberg, Brady R et al. (2018) Reversing the direction of galvanotaxis with controlled increases in boundary layer viscosity. Phys Biol 15:036005
Sameni, Sara; Malacrida, Leonel; Tan, Zhiqun et al. (2018) Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by Spectral Phasor Analysis. Sci Rep 8:734
Konstorum, Anna; Lowengrub, John S (2018) Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model. J Theor Biol 439:86-99
Yan, Huaming; Konstorum, Anna; Lowengrub, John S (2018) Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth. Bull Math Biol 80:1404-1433
Ranjit, Suman; Malacrida, Leonel; Gratton, Enrico (2018) Differences between FLIM phasor analyses for data collected with the Becker and Hickl SPC830 card and with the FLIMbox card. Microsc Res Tech 81:980-989
Kim, Seong M; Nguyen, Tricia T; Ravi, Archna et al. (2018) PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells. Cancer Discov 8:866-883
Staaf, Elina; Hedde, Per Niklas; Bagawath Singh, Sunitha et al. (2018) Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A. Sci Signal 11:

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