北京大学基础医学院

院长论坛

 

报告题目：Cellular Biochemical Activity Architecture for Signal Sensing and Processing

报 告 人：Jin Zhang, Ph.D.

University of California, San Diego

时      间：2019 年3 月27 日（星期三）上午10:30

地      点：生化楼三层中厅

主 持 人 ：张勇研究员

报告简介：

Intracellular signaling pathways in the brain play a central role in regulating neuronal activity and synaptic plasticity. We have developed a series of fluorescent biosensors to probe the spatiotemporal regulation of signaling molecules, such as protein kinases, phosphatases and second messengers, in living systems. In this talk, I will discuss some of the imaging technologies; and focus on cAMP/PKA and calcium signaling pathways and present studies where we combined genetically encoded fluorescent biosensors, superresolution imaging, targeted biochemical perturbations and mathematical modeling to probe the biochemical activity architecture of the cell.

 

Representative Publications:

1. DiPilato LM, Cheng X, and Zhang J. Fluorescent Indicators of cAMP and Epac Activation Reveal Differential Dynamics of cAMP Signaling within Discrete Subcellular Compartments. Proc. Natl. Acad. Sci. USA 2004; 101: 16513-16518.

2. Zhou X, Clister TL, Lowry PR, Seldin MM, Wong GW and Zhang J. Dynamic Visualization of mTORC1 Activity in Living Cells. Cell Rep. 2015, 10(10): 1767-1777. PMCID: PMC4567530

3. Ross BL, Tenner B, MarkwardtML, ZvimanA, ShiG, Kerr JP, McFarlandJJ, Mauban JR, Ward CW, Rizzo MA？ and Zhang J？. Single-Color, Ratiometric Biosensors for Detecting Signaling Activities. ？Co-corresponding authors. eLife, 2018, 7: e35458.

4. Mehta S？*, Zhang Y*, Roth RH*, Zhang JF, Mo A, Tenner B, Huganir RL？, and Zhang J？. A Suite of Single-fluorophore Biosensors for Sensitive and Multiplexed Detection of Signaling Activities. *Equal contribution. ？Co-corresponding authors. Nat. Cell Biol. 2018, 20(10):1215-1225.

5. Sample V*, DiPilato LM*, Yang J*, Ni Q1, Saucerman JJ？and Zhang J？. Regulation of Nuclear PKA revealed by spatiotemporal manipulation of cAMP. *Equal contribution. ？Co-corresponding authors.Nature Chem. Biol. 2012; 8(4): 375-82.PMCID: PMC3307945
Summary: We developed a new method of using bicarbonate-activatable and genetically targetable soluble adenylyl cyclase to control the location, kinetics and magnitude of the cAMP signal. Using this method in conjunction with fluorescence imaging and mechanistic modeling, we uncovered the activation of a resident pool of PKA holoenzyme in the nuclei of HEK-293 cells, modifying the existing dogma of nuclear cAMP-PKA signaling.

6. Sample V, Ni Q, Mehta S, Inoue T, Zhang J. Controlling Enzymatic Action in Living Cells with a Kinase-Inducible Bimolecular Switch. ACS Chem. Biol. 2013; 8(1): 116-21. PMCID: PMC3549020

7. Miyamoto T？, Rho E, Sample V, Akano H, Magari M, Ueno T, Gorshkov K, Chen M, Tokumitsu H, Zhang J？, and Inoue T？. Compartmentalized AMPK signaling illuminated by genetically encoded molecular sensors and actuators. ？Co-corresponding authors. Cell Rep. 2015, 11(4):657-70. PMCID: PMC4417068

8. Dedecker P？, Mo GCH, Dertinger T, and Zhang J？. Widely accessible method for superresolution fluorescence imaging of living systems.？Co-corresponding authors. Proc. Natl. Acad. Sci. USA 2012; 109(27): 10909-14.PMCID: PMC3390831

9. Dedecker P, Duwé S, Neely RK, and Zhang J. Localizer: fast, accurate, open-source, and modular software package for superresolution microscopy.  J. Biomed. Opt. 2012; 17(12): 126008. PMCID: PMC3512108

10. Hertel F, Mo GCH, Duwé S, Dedecker P, and Zhang J. RefSOFI for Mapping Nanoscale Organization of Protein-protein Interactions in Living cells. Cell Rep.2016, 14(2):390-400. PMCID: PMC4870019

11. Mo GCH, Ross B, Hertel F, Manna P, Yang X, Greenwald E, Booth C, Plummer AM, Tenner B, Chen Z, Wang Y, Kennedy EJ, Cole PA, Fleming KG, Palmer A, Jimenez R, Xiao J, Dedecker P, and Zhang J. Genetically-Encoded Biosensors for Visualizing Live-cell Biochemical Activity at Superresolution. Nat. Met. 2017; 14(4): 427-434. PMCID: PMC5388356

12. Newman RE*, Hu J*, Rho H*, Xie Z*, Woodard C, Neiswinger J, Hwang W, Shirley M, Hu S, Cooper C, Jeong JS, Wu G, Lin J, Gao X, Ni Q, Ji H, Desiderio S, Dalby KN, Birnbaum MJ, Cole PA, Knapp S, Ryazanov A, Zack DJ, Blackshaw S, Pawson T, Gingras A, Pandey A, Turk BE, Zhang J？, Zhu H？, Qian J？. Construction of human activity-based phosphorylation networks. *Equal contribution. ？Co-corresponding authors. Mol. Syst. Biol. 2013; 9:655. PMCID: PMC3658267

13. Hu J*, Rho HS*, Newman RH*, Hwang W, Neiswinger J, Zhu H？, Zhang J？, Qian J？. Global analysis of phosphorylation networks in humans. *Equal contribution. ？Co-corresponding authors. Biochim Biophys Acta. 2013, S1570-9639(13)00122-2. PMCID: PMC3815481

14. Hu J, Rho HS, Newman RH, Zhang J, Zhu H, Qian J. PhosphoNetworks: a database for human phosphorylation networks.  Bioinformatics 2014, 30(1):141-2. PMCID: PMC3866559

15. Hu J, Neiswinger J, Zhang J, Zhu H, Qian J. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction. PLoS Comput Biol. 2015, 11(9): e1004508.

16. Ni Q*, Ganesan A*, Aye-Han N*, Gao X, Allen MD, Levchenko A？, and Zhang J？. Signaling Diversity of PKA via a Ca2+-cAMP-PKA Oscillatory Circuit. *Equal contribution. ？Co-corresponding authors. Nature Chem. Biol. 2011; 7(1):34-40. PMCID: PMC3073414

17. Gao X, Lowry P, Zhou X, Depry C, Wei Z, Wong GW, and Zhang J.PI3K/Akt signaling requires spatial compartmentalization in plasma membrane microdomains. Proc. Natl. Acad. Sci. USA 2011; 108(35): 14509-14. PMCID: PMC3167518

18. Mehta S, Aye-Han N, Ganesan A, Oldach L, Gorshkov K, and Zhang J. Calmodulin-controlled Spatial Decoding of Oscillatory Ca2+ Signals by Calcineurin. eLife, 2014, 3: e03765. PMCID: PMC4141273

19. Gorshkov K, Mehta S, Ramamurthy S, Ronnett GV, Zhou F-Q, Zhang J. AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons. Nature Chem. Biol. 2017; 13(4): 425-431. PMCID: PMC5362298

 

欢迎师生参加！