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integrated mechanobiology of integrin-mediated phagocytosis

integrated mechanobiology of integrin-mediated phagocytosis

By In Aiv Internship On August 20, 2019

Internship title: integrated mechanobiology of integrin-mediated phagocytosis

Name: Biology of Phagocytes
Affiliation: Institut Cochin (Inserm U1016, CNRS UMR8104, Université Paris Descartes)
Address: 22, rue Méchain 75014 Paris
E-mail: Florence.niedergang@inserm.fr

LAB Director
Name: Florence Niedergang
Phone number: 0033140516421
E-mail: florence.niedergang@inserm.fr

Name: Florence Niedergang
Phone number: 0033140516421
E-mail: florence.niedergang@inserm.fr

Subject Keywords: Phagocytosis
Traction force microscopy

Tools and methodologies: fluorescence microscopy
traction force microscopy
Summary of lab’s interests: The laboratory has a long time interest in phagocytosis, the mechanism of uptake and degradation of invading microorganisms or debris that is crucial for bacterial clearance and the resolution of inflammation. Our first goal is to dissect the mechanisms used by phagocytes, in particular the coordinated activities of signaling pathways, membrane trafficking and cytoskeleton dynamics. Second, we analyze how viral infections of macrophages impair their phagocytic and activation functions and hence promote the development of bacterial super-infections.
Project summary: During phagocytosis, actin polymerization drives membrane deformation and phagosome cup formation, which is further modulated by the mechanics of the particle itself and cell adhesion properties. The project focuses on actin-binding proteins, as mechanosensitive hubs at the center of feedback loops that control anchoring to the actin cytoskeleton and activation of the integrins during phagocytosis. Cell biology and biochemistry work has already allowed the team to identify new potential actin regulators. The relative contribution of these factors to phagocytosis will be assessed by functional inhibition or expression of mutants. In addition, the candidate will use a recently developed microscopy approach including an innovative traction force microscopy (TFM) element. This work will contribute to mechanistic studies of integrin-mediated immune cell processes.
Interdisciplinary aspect of the project: The project is performed in collaboration with Christophe Le Clainche (I2BC, Gif-sur-Yvette) who developed an elegant in vitro microscopy assay, to reconstitute and characterise the actomyosin-dependent mechanosensitive machineries with pure proteins on geometrically-defined micropatterned surfaces. This collaboration has enabled the identification of previously unknown actin binding partners active during integrin-mediated phagocytosis. The host lab has developed an original traction force microscopy method to analyse phagocytosis by macrophages, in addition to classical cell biology approaches. The project is part of an ambitious project that includes theoretical modelling of integrin-mediated phagocytosis by Jian Liu (NIH, USA).