Kristina Ganzinger Group

Single-molecule imaging of immune receptor organisation & immune cell membrane models 

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Our Focus

Signaling processes between various immune cells involve large-scale spatial reorganization of receptors and signaling molecules within the cell-cell junctions. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long-range directed transport are all key regulatory mechanisms. Our group’s approach is based on advanced microscopy and on synthetic biology. We combine signaling pathway reconstitution with single-molecule biophysics to understand how immune cells communicate with each other: how do immune cells use molecular signaling pathways to transmit, process, and respond to information, both precisely and unambiguously? Currently, most projects in the lab use a hybrid in vitro-in vivo approach, interfacing in vitro cell surface models with immune cells. We use this approach to study the spatiotemporal reorganization of T-cell signaling molecules in natural signaling networks, but also for and man-designed signaling molecules in immunotherapeutics against cancer. 

About Kristina Ganzinger

My Research

Kristina Ganzinger received her PhD in Physical Chemistry from the University of Cambridge (United Kingdom) in 2015, under the guidance of Sir Prof. David Klenerman. After a postdoc at the Max Planck Institute for Biochemistry (Germany) with Prof. Petra Schwille, she began her current position as tenure-track group leader at the NWO physics institute AMOLF (Netherlands) in 2018.  

Her main aim is to unravel how immune cells communicate with each other, both in natural and immunotherapy contexts: how do immune cells use molecular signaling pathways to transmit, process, and respond to information, both precisely and unambiguously? 

Her lab’s approach is to address these questions by (1) in vitro reconstitution in model-membrane systems (“minimal cells”) and (2) pairing these studies with live- cell experiments. They use custom microscopy, quantitative data analysis and, in collaboration, predictive mathematical modelling to understand the underlying molecular mechanisms, and for this continuously develop new (single-molecule) microscopy methods. Her group is passionate about open access science and sharing methods via github (see https://github.com/GanzingerLaband https://ganzingerlab.github.io/K2TIRF/index.html) and pre-prints. 

Kristina’s current research addresses: 

  • Signaling pathway reconstruction: we use a hybrid in vitro-in vivo approach, interfacing in vitro cell surface models with immune cells. In her previous research, Kristina found that the spatiotemporal reorganization of T-cell signaling molecules is key to initiate and control T cell signalling. 
  • Engineering signaling pathways: Her group pioneers the application of the same biophysics approach to understand the man-designed signaling networks in immunotherapeutics against cancer e.g., chimeric antigen receptors (CARs) signaling, with the aim of making these therapies more effective. 
  • Signaling in synthetic cells: Her group develops methods for the in vitro reconstitution of signaling molecules in lipid vesicles, the groundwork for her goal to develop synthetic cells that communicate with each other and with living cells. 
Awards
  • Jean Corsan Prize from the UK’s largest Alzheimer’s research foundation (ARUK) (2015) 
  • Women in Science Excel grant (NWO, 2017) 
  • Pieter Langerhuizen bate from the Koninklijke Hollandsche Maatschappij der Wetenschappen (2020) 
  • Vidi grant (2020) 
  • Coordinator of the EIC Pathfinder Open Consortium “REPRESSIT” on the development of novel checkpoint immunotherapies (2022) 
  • Elected member of De Jonge Akademie / Young Academy of KNAW (from 2023).
Key Publications
  1. Niederauer C, et al. DNA-PAINT single-particle tracking (DNAPAINT-SPT) enables extended single-molecule studies of membrane protein interactions. Nat Commun 14, 4345 (2023). 
  1. L Van de Cauter et al, Optimized cDICE for efficient reconstitution of biological systems in giant unilamellar vesicles, ACS Syn Biol 10, 1690 (2021)  
  1. RA Fernandes*, KA Ganzinger* et al, A cell topography-based mechanism for ligand discrimination by the T cell receptor. Proc Natl Acad Sci USA, 116, 14002 (2019) 
  1. KA Ganzinger and P Schwille, More from less–bottom-up reconstitution of cell biology. J Cell Sci 132, jcs227488 (2019) 
  1. Chang* VT, Fernandes* RA, Ganzinger* KA, Lee* SF, et al. Initiation of T cell signaling by CD45 segregation at ‘close contacts’. Nat Immunol 17: 574–582 (2016). 

Members

Kristina Ganzinger
Oncode Investigator
Chikim (Chi)Nguyen
Phd student
Gerard Linares
Postdoc
Megan Farrell
Post-doc
Nebojsa Jukic
Postdoc
Raquel Martinez Gonzalez
Postdoc
Stefanos Zoidis
PhD student
Tom Aarts
PhD student
Tom Evers
PhD