A02: SFB 1328

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

E-Mail: b.diercks©uke.de
www: Dept. of Biochemistry and Molecular Cell Biology, University Medical Centre HamburgEppendorf (UKE)

Prof. Dr. René Werner

E-Mail: r.werner©uke.de
www: UKE - Institut für Angewandte Medizininformatik - Image Processing

PD Dr. Björn-Philipp Diercks

Selected publications (*equal contribution)

Winterberg KJ, Schwentner V, Gu F, Möckl F, Li G, Bauche A, Etzold S, Rosche A, Weiß M, Thuille N, Förster F, Woelk L, Werner R, Kovacevic D, Fehse B, Kurelic R, Nawrocki M, Huber S, Mittrücker HW, Meier C, Müller CE, Baier G, Skålhegg BS, de Deken X, Wahl-Schott C, Mair T, Siebels B, Cugota Canals R, Odoardi F, Lodygin D, Flügel A, Nikolaev VO, Diercks BP, Guse AH. Multiple signaling events are required for NAADP synthesis by DUOX2 and formation of Ca²⁺ microdomains to initiate T cell activation. Sci Signal. 2026 Jan 13;19(920):eadp4326.
Jaeckstein MY, Miegel L, Behrens J, Stähler T, Diercks BP, Heine M, Koch-Nolte F, Heeren J. The Purinergic Receptor P2X5 Modulates Glucose Metabolism and Expression of Thermogenic Genes in Brown Adipose Tissue. Int J Mol Sci. 2025 Jul 4;26(13):6474.
Gerlach F, Möckl F, Kovacevic D, Brock VJ, Winzer R, Meyer L, Lohr D, Woelk LM, Tolosa E, Werner R, Diercks BP. Imaging Initial Ca²⁺ Microdomains in Primary T Cells. J Vis Exp. 2024 Oct 4;(212).
Krukenberg S, Möckl F, Weiß M, Dekiert P, Hofmann M, Gerlach F, Winterberg KJ, Kovacevic D, Khansahib I, Troost B, Hinrichs M, Granato V, Nawrocki M, Hub T, Tsvilovskyy V, Medert R, Woelk LM, Förster F, Li H, Werner R, Altfeld M, Huber S, Clarke OB, Freichel M, Diercks BP, Meier C*, Guse AH*. MASTER-NAADP: a membrane permeable precursor of the Ca²⁺mobilizing second messenger NAADP. Nat Commun. 2024 Sep 13;15(1):8008.
Woelk LM, Kovacevic D, Husseini H, Förster F, Gerlach F, Möckl F, Altfeld M, Guse AH, Diercks BP, Werner R. DARTS: an open-source Python pipeline for Ca²⁺ microdomain analysis in live cell imaging data. Front Immunol. 2024 Jan 11;14:1299435.
Brock VJ, Lory NC, Möckl F, Birus M, Stähler T, Woelk LM, Jaeckstein M, Heeren J, Koch-Nolte F, Rissiek B, Mittrücker HW, Guse AH, Werner R, Diercks BP. Time-resolved role of P2X4 and P2X7 during CD8⁺ T cell activation. Front Immunol. 2024 Feb 15;15:1258119.
Siracusa F, Schaltenberg N, Kumar Y, Lesker TR, Steglich B, Liwinski T, Cortesi F, Frommann L, Diercks BP, Bönisch F, Fischer AW, Scognamiglio P, Pauly MJ, Casar C, Cohen Y, Pelczar P, Agalioti T, Delfs F, Worthmann A, Wahib R, Jagemann B, Mittrücker HW, Kretz O, Guse AH, Izbicki JR, Lassen KG, Strowig T, Schweizer M, Villablanca EJ, Elinav E, Huber S, Heeren J, Gagliani N. Short-term dietary changes can result in mucosal and systemic immune depression. Nat Immunol. 2023 Sep;24(9):1473-1486.
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.
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.
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.

Prof. Dr. René Werner

Selected publications (* equal contribution)

Winterberg KJ, Schwentner V, Gu F, Möckl F, Li G, Bauche A, Etzold S, Rosche A, Weiß M, Thuille N, Förster F, Woelk L, Werner R, Kovacevic D, Fehse B, Kurelic R, Nawrocki M, Huber S, Mittrücker HW, Meier C, Müller CE, Baier G, Skålhegg BS, de Deken X, Wahl-Schott C, Mair T, Siebels B, Cugota Canals R, Odoardi F, Lodygin D, Flügel A, Nikolaev VO, Diercks BP, Guse AH. Multiple signaling events are required for NAADP synthesis by DUOX2 and formation of Ca²⁺ microdomains to initiate T cell activation. Sci Signal. 2026 Jan 13;19(920):eadp4326.
Gerlach F, Möckl F, Kovacevic D, Brock VJ, Winzer R, Meyer L, Lohr D, Woelk LM, Tolosa E, Werner R, Diercks BP. Imaging Initial Ca²⁺ Microdomains in Primary T Cells. J Vis Exp. 2024 Oct 4;(212).
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
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.
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.
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.
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.
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.
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).
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.