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.


Main questions of the lab are currently:
•    How is protrusive activity regulated at the leading edge of dendritic cells and lymphocytes? How do different extracellular constraints like the form of chemokine presentation, mechanical forces and the geometry and molecular composition of the extracellular substrate, affect locomotion.
•    How is cytoskeletal activity translated into actual locomotion? This includes the investigation of transmembrane force coupling receptors but also locomotion by other means like physical deformation of the cell body.
•    How are guidance cues (chemokines) presented in the tissue and how do they polarizes and guide the leukocytes.
•    How do leukocytes traverse tissue bounderies like endothelial / epithelial layers and extracellular matrix barriers like basement membranes.


Open positions in the Sixt Lab:
We have several openings for Postdocs and PhD students. If you are interested in joining our lab, please send your application (incl. CV, publication list, 3 reference letters) to E-Mail . Cell-biologists, immunologists and biophysicists are particularly encouraged to apply. Students are also encouraged to apply at the IST Austria Grad School.


Key publications
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

Riedl J, Flynn KC, Raducanu A, Gärtner F, Beck G, Bösl M, Bradke F, Massberg S, Aszodi A, Sixt M*, Wedlich-Söldner R*
Lifeact mice for studying F-actin dynamics
Nat Methods. 2010 Mar;7(3):168-9

Pflicke H, Sixt M
Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
J Exp Med, 2009 Dec 21;206(13):2925-35

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

Lammermann T, Renkawitz J, Wu X, Brakebusch C, Sixt M
Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration.
Blood, 2009 Jun 4;113(23):5703-10

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):51-5

Riedl J, Crevenna AH, Kessenbrock K, Yu JH, Neukirchen D, Bista M, Bradke F, Jenne D, Holak TA, Werb Z, Sixt M*, Wedlich-Soldner R*
Lifeact: a versatile marker to visualize F-actin.
Nat Methods, 2008 Jul;5(7):605-7

Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L
The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node.
Immunity, 2005 Jan;22(1):19-29


Reviews
Nourshargh S, Hordjik P, Sixt M
Regulation of leukocyte motility: through venular walls and beyond
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