Morphodynamics of Immune Cells

Michael Sixt

Michael Sixt's laboratory is interested in morphodynamic processes both at the cellular and at the tissue level. We mainly focus on the immune system and try to understand the molecular and mechanical principles underlying leukocyte dynamics during processes such as migration and intercellular communication. Here we work at the interface of cell biology, immunology and biophysics and currently investigate how the cytoskeleton generates force to deform the cell body, how this force is transduced to the extracellular environment and how the cells are polarized and guided within tissues. To obtain a holistic view of the process we are also studying tissue architecture as well as the distribution and presentation of guidance cues (chemokines) within these tissues. We developed a number of in vitro tools that allow us to observe cytoskeletal dynamics in real time using different life cell imaging approaches. These are all based on advanced light microscopy like total internal reflection, fast confocal and multiphoton technology. We combine these approaches with genetic and pharmacological interference as well as substrate manipulations like surface micropatterning and microfluidics. A general aim of the lab is to test in vitro findings also in the context of living tissues.  To this end we also developed ex vivo (tissue explant) and in vivo imaging setups that allow us to monitor leukocytes together with their physiological environment. Finally we are also interested to test the implications of our findings for physiological immune responses.

Contact
Michael Sixt
Institute of Science and Technology Austria (IST Austria)
Am Campus 1
A – 3400 Klosterneuburg

Phone: +43 (0)2243 9000-3801
E-mail: michael.sixt@remove-this.ist.ac.at

CV and publicaton list

Sixt Group website

Assistant
Nicole Hotzy

Phone: +43 (0)2243 9000-1032
E-mail: nicole.hotzy@remove-this.ist.ac.at

Team

  • Miroslav Hons, Postdoc
  • Eva Kiermaier, Postdoc
  • Aglaja Kopf, Student Intern
  • Alexander Leithner, PhD Student
  • Christine Moussion, Postdoc
  • Jörg Renkawitz, Postdoc
  • Anne Reversat, Postdoc
  • Verena Ruprecht, Joint Postdoc with Heisenberg Group
  • Jan Schwarz, PhD Student
  • Kari Vaahtomeri, Postdoc
  • Ingrid de Vries, Technician

Current Projects

  • Environmental control of leukocyte migration
    We are investigating how different extracellular constraints like the form of chemokine presentation, mechanical forces and the geometry and molecular composition of the extracellular substrate, affect leukocyte locomotion.
  • Cellular force generation and transduction
    We ask how cytoskeletal activity is translated into actual locomotion. This includes transmembrane force coupling receptors but also locomotion by other means like physical deformation of the cell body.
  • Invasion of tissue barriers
    How do leukocytes traverse tissue boundaries like endothelial / epithelial layers and extracellular matrix
  • Organization of cell-cell contacts How does the cytoskeleton organize cell to cell encounters in immunological synapses

Selected Publications

  • Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler DF, Luther SA, Bollenbach T, Sixt M. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science, 2013 Jan 18;339(6117):328-32
  • Schumann K, Lämmermann T, Bruckner M, Legler DF, Polleux J, Spatz JP, Schuler G, Förster R, Lutz MB, Sorokin L, Sixt M. Immobilized chemokine fields and soluble chemokine gradients shape migration patterns of dendritic cells. Immunity, 2010 May 28;32(5):703-13
  • Renkawitz J, Schumann K, Weber M, Lämmermann T, Pflicke H, Polleux J, Spatz JP, Sixt M. Adaptive force transmission in amoeboid cell migration. Nat Cell Biol, 2009 Dec;11(12):1438-43
  • Lämmermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Söldner R, Hirsch K, Keller M, Förster R, Critchley DR, Fässler R, Sixt M. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature, 2008 May 1;453(7191):51-55

Selected Reviews

  • Nourshargh S, Hordjik P, Sixt M. Regulation of leukocyte motility: through venular walls and beyon. Nat Rev Mol Cell Biol, 2010 May;11(5):366-78
  • Lämmermann T, Sixt M. Mechanical modes of amoeboid cell migration. Curr Opin Cell Biol, 2009 Oct;21(5):636-44
  • Lämmermann T, Sixt M. The microanatomy of T-cell responses. Immunol Rev, 2008 Feb;221:26-43

Career

2013 Professor, IST Austria
2010-2013 Assistant Professor, IST Austria
2008-2010 Endowed Professor, Peter Hans Hofschneider Foundation for Experimental Biomedicine
2005-2010 Group Leader, Max-Planck Institute, Martinsried, Germany
2003-2005 Postdoc, Institute for Experimental Pathology, Lund, Sweden
2004 MD, University of Erlangen, Germany
2002 Full approbation in human medicine

Selected Distinctions

2013 European Biophysical Societies Association (EBSA) Young Investigator Medal
2013 Elected member of the "Junge Kurie" (Young Academy) of the Austrian Acadamy of Sciences (ÖAW)
2012 HFSP Grant
2011 ERC Starting Grant
2011 FWF START Award
2008 Endowed Professor of Peter Hans Hofschneider Foundation
2003 Novartis research price for best medical dissertation at University of Erlangen

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