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Dissecting a Novel Mechanism of Cell Motility

Cell motility is essential for many biological processes, including development and pathogenesis. Thus, the molecular mechanisms underlying this process have been intensively studied in many cell systems, for example, leukocytes,... ver más

31/12/2015

CNRS

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2015-12-31 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cell motility is essential for many biological processes, including development and pathogenesis. Thus, the molecular mechanisms underlying this process have been intensively studied in many cell systems, for example, leukocytes, amoeba and even bacteria. Intriguingly, bacteria are also able to move across solid surfaces (gliding motility) like eukaryotic cells by a process that has remained largely mysterious. The emergence of bacterial cell biology: the discovery that the bacterial cell also has a dynamic cytoskeleton and specialized subcellular regions now provides new research angles to study the motility mechanism. Using cell biology approaches, we previously suggested that the mechanism may be akin to acto-myosin-based motility in eukaryotic cells and proposed that bacterial focal adhesion complexes also power locomotion. In this project, we propose two complementary research axes to define both the mechanism and its spatial regulation in the cell at molecular resolution. Using the model motility bacterium Myxococcus xanthus, we first propose to develop a toolbox of biophysical and cell biology assays to analyze the motility process. Specifically, we will construct a Traction Force Microscopy assay designed to image the motility forces directly by live moving cells and use microfluidics to quantitate the secretion of a mucus that may participate directly in the motility process. These assays, combined with a newly developed laser trap system to visualize dynamic focal adhesions in the cell envelope, will be instrumental not only to define new features of the motility process, but also to study the function of novel motility genes which may encode the components of the elusive motility engine. This way, we hope to establish the mechanism and structure function relationships within an entirely novel motility machinery. In a second part, we propose to investigate the mechanism that controls a polarity switch, allowing M. xanthus cells to change their direction of movement. We have previously shown that dynamic motility protein pole-to-pole oscillations convert the initial leading cell pole into the lagging pole. Here, we propose that like in a eukaryotic cells, a bacterial counterpart of small GTPases of the Ras superfamily, MglA controls the polarity cycle. To test this hypothesis, we will study both the MglA upstream regulation and the MglA downstream effectors. We thus hope to establish a model of dynamic polarity control in a bacterial

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