Job announcemnet
------------------------------------------------------------------------------------------------------------------------
Interdisciplinary Center of Nanoscience of Marseille (CINaM), France

PhD - Physics of the mucociliary clearance

Application deadline: April 10th 2017
------------------------------------------------------------------------------------------------------------------------
[printable version .pdf]

Thesis subject

Name of the laboratory: Interdisciplinary Center of Nanoscience of Marseille (CINaM)
Thesis advisor: Dr. Annie Viallat
Email and address: viallat@cinam.univ-mrs.fr
CINaM CNRS UMR7325, Campus de Luminy, Case 913 F-13288 Marseille cedex 9
Co-advisor: Pr. Pascal Chanez

Subject’s title: Physics of the mucociliary clearance

Subject description:
Mucociliary clearance is an essential mechanism of lung protection, which is strongly impaired in severe asthma and chronic obstructive pulmonary disease. It consists in the transport at the surface of the airway epithelium (and further elimination by swallowing) of a protective mucus layer. Mucus is propelled by the asymmetric beating of microscopic cilia located on ciliated cells, a type of epithelial cells (Figure). During its forward motion, a cilium performs a fast effective stroke and its tip immersed in mucus propels it forward. The slow recovery stroke of a cilium occurs below the mucus layer, within a swollen gel called the periciliary layer (1). The mucociliary system is a remarkable coupled system. Mucus transport on a macroscopic scale requires a coordinated motion of all cilia at the whole epithelium’s surface. The physics of the integrated mucociliary system has been little studied and many questions, such as the density and spatial repartition of ciliated cells, the coordination in direction and phase of cilia beats required to ensure an efficient macroscopic mucus transport are open.

The PhD project is focused on the physical analysis of ciliary activity, fluid transport and mucociliary coupling on reconstituted cultures of human bronchial epithelium at air-liquid interface obtained by biopsies from controls and patients with chronic airway diseases (2). Experiments rely on techniques of microscopy (videomicroscopy, confocal microscopy).  A first doctoral work has been done with very novel results that are currently under review for publication[3]. The student will explore the conditions on cilia density and spatial organization, the physical parameters of cilia beats and their collective coordination, which control the long-distance transport of viscoelastic mucus and Newtonian fluids (domains of transport, mucus velocity). He will study the macroscopic force and the dissipated power that are generated by local cilia beats.

In collaboration with biologists and medical doctors (D. Gras and P. Chanez) the student will address the question of the active regulation of ciliogenesis and cilia beat directions under the effect of the mechanical force exerted by the mucus on cilia. Finally, the findings will be confronted with the clinical situations of patients with severe asthma and chronic obstructive pulmonary disease.

The project is funded by ANR in collaboration with Pr. Pascal Chanez, lung specialist (Marseille) and a small company in clinical assays (Montpellier).

The PhD student will work under the supervision of Dr. Annie VIALLAT. Collaboration with Dr. J. Favier, Dr. U. D’Ortona and Pr. M. Jaeger (M2P2, Marseille) will be developed on numerical simulations and theoretical approaches.

Bibliography:

[1] Button B, et al. (2012) A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 337(6097):937–41.

[2] Gras D, et al. (2012) An ex vivo model of severe asthma using reconstituted human bronchial epithelium. J Allergy Clin Immunol 129(5):1259–1266.e1

[3] Khelloufi, Gras, Chanez, Viallat, Relation between forces applied by beating cilia and mucus transport in reconstituted bronchial epithelium. Application to severe asthma. Submitted to PNAS

inks to submit applications
http://doc2amu.univ-amu.fr/en/hypersecretion-in-severe-airway-diseases-an-integrated-biophysical-approach-of-the-mucociliary-2

and to have information on the DOC2AMU program:
http://doc2amu.univ-amu.fr/en/what-is-doc2amu

The project is partly funded by the European Commission, appliquants must come from outside of France


© 29.03.2017 Deutsche Zoologische Gesellschaft e.V., DZG