Supervisors:PhD Director: Renaud Poincloux – Phagocyte architecture and dynamics Research Unit: IPBS, CNRS, Toulouse, France
PhD co-supervision: Marion Jasnin – Max Planck Institute of Biochemistry, Munich, Germany
Macrophages do not only play a beneficial role in our immunity. Indeed, the massive tissue infiltration of macrophages derived from blood monocytes has a deleterious effect in most cancers and chronic inflammations, among other pathologies. It is therefore important to dissect the molecular mechanisms involved in the deleterious infiltration of tumor-associated macrophages in order to modulate it. In dense tumors, macrophages use the mesenchymal mode of migration, which requires proteolysis of the extracellular matrix, and the formation of adhesion structures called podosomes.
The proposed project is part of an interdisciplinary research program that combines cutting-edge and innovative techniques in optical and electron imaging, cell mechanics and materials science. It will build on our complementary expertise in podosome mechanobiology and cryo-electron tomography in situ to decipher the influence of nanoscale substrate topography on macrophage podosomes, the molecular mechanism involved in macrophage topography sensing and its importance for the infiltration of tumor-associated macrophages.
Key words: tumor-associated macrophages; nano-topography; cryo-electron tomography; actin cytoskeleton; BAR-domain proteins