A02

A02 Project movie

A02

From Diercks, B.-P. et al. (2018). ORAI1, STIM1/2, and RYR1 shape subsecond Ca2+ microdomains upon T cell activation. Sci. Signal. 11, eaat0358.

Activation of T cells is closely related to the occurrence of Ca2+ microdomains. Our project aims to unravel the interplay of the complementary players during early T cell activation. Here, we focus on the formation of antigen dependent Ca2+ micro- and even nanodomains, the characterization of ‘pure’ NAADP evoked Ca2+ signals as well as the visualization of the initial ATP concentration surrounding single T cells. To resolve and analyze associated Ca2+ micro-/nanodomains, the project develops and integrates innovative artificial intelligence and image processing algorithms and high-speed super-resolution live cell imaging.

PD Dr. Björn-Philipp Diercks

Selected publications (*equal contribution)

 

  1. Weiß M, Hernandez LC, Gil Montoya DC, Löhndorf A, Krüger A, Kopdag M, Uebler L, Landwehr M, Nawrocki M, Huber S, Woelk LM, Werner R, Failla AV, Flügel A, Dupont G, Guse AH, Diercks BP. Adhesion to laminin-1 and collagen IV induces the formation of Ca2+ microdomains that sensitize mouse T cells for activation. Sci Signal. 2023 Jun 20;16(790):eabn9405.
  2. Brock VJ, Wolf IMA, Er-Lukowiak M, Lory N, Stähler T, Woelk LM, Mittrücker HW, Müller CE, Koch-Nolte F, Rissiek B, Werner R, Guse AH, Diercks BP. P2X4 and P2X7 are essential players in basal T cell activity and Ca2+ signaling milliseconds after T cell activation. Sci Adv. 2022 Feb 4;8(5):eabl9770.
  3. Gu F, Krüger A, Roggenkamp HG, Alpers R, Lodygin D, Jaquet V, Möckl F, Hernandez C LC, Winterberg K, Bauche A, Rosche A, Grasberger H, Kao JY, Schetelig D, Werner R, Schröder K, Carty M, Bowie AG, Huber S, Meier C, Mittrücker HW, Heeren J, Krause KH, Flügel A, Diercks B-P*, Guse AH*. Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation. Science Signal. 2021; 14 eabe3800.
  4. Roggenkamp HG, Khansahib I, Hernandez C LC, Zhang Y, Lodygin D, Krüger A, Gu F, Möckl F, Löhndorf A, Wolters V, Woike D, Rosche A, Bauche A, Schetelig D, Werner R, Schlüter H, Failla AV, Meier C, Fliegert R, Walseth TF, Flügel A, Diercks B-P*, Guse AH*. HN1L/JPT2: A signaling protein that connects NAADP generation to Ca2+ microdomain formation. Science Signal. 2021; 14:eabd5647.
  5. Woelk LM, Kannabiran SA, Brock VJ, Gee CE, Lohr C, Guse AH, Diercks B-P, Werner R. Time Dependent Image Restoration of Low-SNR Live-Cell Ca2+ Fluorescence Microscopy Data. Int. J. Mol. Sci. 2021; 22, 11792.
  6. Löhndorf A, Hosang L, Dohle W, Odoardi F, Waschkowski SA, Rosche A, Bauche A, Winzer R, Tolosa E, Windhorst S, Marry S, Flügel A, Potter BVL, Diercks B-P*, Guse AH*. 2-Methoxyestradiol and its derivatives inhibit store-operated Ca2+ entry in T cells: identification of a new and potent inhibitor. BBA Mol Cell Res. 2021; 118988.
  7. Diercks BP, Werner R, Schetelig D, Wolf IMA, Guse AH (2019) High-Resolution Calcium Imaging Method for Local Calcium Signaling. Methods Mol Biol. 1929:27-39.
  8. Diercks BP, Werner R, Weidemüller P, Czarniak F, Hernandez L, Lehmann C, Rosche A, Krüger A, Kaufmann U, Vaeth M, Failla AV, Zobiak B, Kandil FI, Schetelig D, Ruthenbeck A, Meier C, Lodygin D, Flügel A, Ren D, Wolf IMA, Feske S, Guse AH (2018) ORAI1, STIM1/2, and RYR1 shape subsecond Ca2+ microdomains upon T cell activation. Sci Signal 18;11(561).
  9. Diercks BP, Fliegert R, Guse AH (2016) Mag-Fluo4 in T Cells: Imaging of Intra-Organelle Free Ca2+Concentrations. Biochim Biophys Acta Mol Cell Res. 2017 Jun;1864(6):977-986.
  10. Wolf IMA*, Diercks BP*, Gattkowski E, Czarniak F, Kempski J, Werner R, Schetelig D, Mittrücker HW, Schumacher V, von Osten M, Lodygin D, Flügel A, Fliegert R, Guse AH (2015) Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor. Sci Signal 8: ra102.

 

 

 

 

PD Dr. René Werner

Selected publications (* equal contribution)

 

  1. Woelk L-M, Kovacevic D, Husseini H, Förster F, Gerlach F, Möckl F, Altfeld M, Guse AH, Diercks B-P, Werner R. DARTS: an open-source Python pipeline for Ca2+ microdomain analysis in live cell imaging data. Front. Immunol. 2024 Jan:14:1299435
  2. Woelk LM, Kannabiran SA, Brock VJ, Gee CE, Lohr C, Guse AH, Diercks B-P, Werner R. Time Dependent Image Restoration of Low-SNR Live-Cell Ca2+ Fluorescence Microscopy Data. Int. J. Mol. Sci. 2021; 22, 11792.
  3. Hadaeghi F, Diercks B-P, Schetelig D, Damicelli F, Wolf IMA, Werner R (2021) Spatio-temporal feature learning with reservoir computing for T-cell segmentation in live-cell Ca2+ fluorescence microscopy. Sci Rep. 2021; 11:8233.
  4. Schmitz R, Madesta F, Nielsen M, Krause J, Steurer S, Krause J, Werner R*, Rösch T*. Multi-scale fully convolutional neural networks for histopathology image segmentation: From nuclear aberrations to the global tissue architecture. Med Image Anal. 2021; 70:101996.
  5. Schmitz R, Werner R, Repici A, Bisschops R, Meining A, Zornow M, Messmann H, Hassan C, Sharma P, Rösch T. Artificial intelligence in GI endoscopy: stumbling blocks, gold standards and the role of endoscopy societies. Gut. 2021; 0:1–4.
  6. Nielsen M, Waldmann M, Frölich AM, Flottmann F, Hristova E, Bendszus M, Seker F, Fiehler J, Sentker T, Werner R. Deep learning-based automated TICI scoring: a timely proof-of-principle study. Stroke 2021; 52:3497-3504.
  7. Madesta F, Schmitz R, Rösch T, Werner R. Widening the focus: biomedical image segmentation challenges and the underestimated role of patch sampling and inference strategies. In: MICCAI 2020, Lecture Notes in Computer Science (LNCS), 2020, Springer, vol. 12264, pp. 289-298.
  8. Diercks BP, Werner R, Schetelig D, Wolf IMA, Guse AH (2019) High-Resolution Calcium Imaging Method for Local Calcium Signaling. Methods Mol Biol. 1929:27-39.
  9. Diercks BP, Werner R, Weidemüller P, Czarniak F, Hernandez L, Lehmann C, Rosche A, Krüger A, Kaufmann U, Vaeth M, Failla AV, Zobiak B, Kandil FI, Schetelig D, Ruthenbeck A, Meier C, Lodygin D, Flügel A, Ren D, Wolf IMA, Feske S, Guse AH (2018) ORAI1, STIM1/2, and RYR1 shape subsecond Ca2+ microdomains upon T cell activation. Sci Signal 18;11(561).
  10. Wolf IMA, Diercks B-P, Gattkowski E, Czarniak F, Kempski J, Werner R, Schetelig D, Mittrücker HW, Schumacher V, von Osten M, Lodygin D, Flügel A, Fliegert R, Guse AH (2015) Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor. Sci Signal 8:ra120.
  11. Werner R, Schmidt-Richberg A, Handels H, Ehrhardt J (2014) Estimation of lung motion fields in 4D CT data by variational non-linear intensity-based registration. Phys Med Biol 59:4247-4260.

Our Team

Dr. Björn-Philipp Diercks

Department of Biochemistry and Molecular Cell Biology

University Medical Center Hamburg-Eppendorf (UKE)

PD Dr. René Werner

Department of Computational Neuroscience

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Franziska Moeckl

 
Department of Biochemistry and Molecular Cell Biology

University Medical Center Hamburg-Eppendorf (UKE)

Dejan Kovacevic

Department of Biochemistry and Molecular Cell Biology

University Medical Center Hamburg-Eppendorf (UKE)

Alumni

Dr. Lena Woelk

 
Department of Computational Neuroscience

University Medical Center Hamburg-Eppendorf (UKE)

Dr. Valerie Brock

 
Department of Biochemistry and Molecular Cell Biology

University Medical Center Hamburg-Eppendorf (UKE)

PD Dr. Insa Wolf

Department of Biochemistry and Molecular Cell Biology

University Medical Center Hamburg-Eppendorf (UKE)

Dr. Daniel Schetelig

Department of Computational Neuroscience

University Medical Center Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de