3 Years Phd Funding In Biophysics: Understanding The Coupling Between Hydrodynamic Forces, Cilia Beating And Tissue Polarity In Mucus Transport By Using An Organ-On-Chip Device

26 Jun 2023

Job Information

Organisation/Company

Aix Marseille University / CNRS

Department

Physics and Engineering of Living Systems

Research Field

Physics » Biophysics

Physics

Researcher Profile

First Stage Researcher (R1)

Country

France

Application Deadline

30 Sep 2023 - 12:00 (Europe/Paris)

Type of Contract

Temporary

Job Status

Full-time

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Is the Job related to staff position within a Research Infrastructure?

Yes

Offer Description

Keywords: physics of living systems, active matter, self-organization, ciliated epithelium, tissue polarity, bronchial epithelium

Context & aim of the project:

The airways are protected from inhaled pollutants and pathogens by a layer of mucus, a complex fluid that is continuously transported along the bronchial walls before being cleared out and swallowed. The mucus is propelled via the continuous beating of millions of microscopic active cilia exposed by the epithelial ciliated cells. This process, called mucociliary clearance, is strongly impaired in chronic respiratory diseases which affect hundreds of millions of people.

From a biophysical point of view, the bronchial epithelium is a complex active system. On top, cilia beat and create local flows in the mucus. The resulting overall flow, in turn, applies a hydrodynamic force on each cilium that could change its beat direction via an active response and thus align with the others to create a directional flow. Underneath, cilia are linked to fibers (cytoskeleton) oriented according to a preferential direction, called Planar Cell Polarity, which results from a spatial organization of the cells in the tissue when submitted to mechanical forces during development.

We want to understand how millions of microscopic active cilia coordinate their beatings to generate a coherent flow over macroscopic distances. Our hypothesis is that the long-range coordination of ciliary beats results from a complex interplay between hydrodynamic forces in the mucus, active cilia and tissue polarity. This interplay needs to be elucidated to understand the transport of mucus in health and disease.

Experimental approach:

The experimental approach relies on various techniques of optical microscopy (videomicroscopy, confocal microscopy…) combined with image processing. We will develop a microfluidics Organ-On-Chip device to grow a human bronchial epithelium under physical constraints that are relevant to probe the biological active response of the system. We will: 1) evaluate to what extent cilia actively reorient in response to a hydrodynamic constraint, and in turn how this modifies the patterning of the tissue polarity, 2) determine mechanical constraints applied on the epithelium needed to create and maintain tissue polarity and in turn constrain the cilia beat directions, by stretching the tissue in the Organ-On-Chip device. This will enable us to establish the relation between mucus transport velocity, mucus rheology, and tissue polarity to determine the critical regime of mucus transport (good mucus clearance, defective clearance, arrest of mucus transport). Experimental data will be used to calibrate a numerical model developed by our collaborators to simulate complex configuration (bronchi geometry…).

Expected profile of the candidate

A Master degree in physics (soft matter, biophysics…) or in biomechanical engineering. The selected PhD student must have a keen interest in interdisciplinary project.

Interdisciplinarity / Scientific environment

This project will be done in the Physics and Engineering of Living Systems department at CINaM, Marseille, France. This is an interdisciplinary project, in collaboration with two other groups - Kodjabachian's lab: Biology of ciliated epithelia and Favier's lab: computational fluid dynamics of biological flows - already involved in the analysis of cilia-driven fluid flows and mucus transport. The three groups have already engaged multiple collaborations and co-authored several publications. The three groups belongs to the CENTURI institute that aims at developing an integrated interdisciplinary community, to decipher the complexity of biological systemsthrough the understanding of how biological function emerges from the organization and dynamics of living systems.

Contacts & how to apply

Send a detailed cv and a cover letter to: Etienne Loiseau - [email protected]

References related to the project:

O Mesdjian et al., Longitudinal to transverse metachronal wave transitions in an In Vitro model of ciliated bronchial epithelium, Physical Review Letters , 2022

E. Loiseau, et al, Active mucus-cilia hydrodynamic coupling drives the self- organisation of human bronchial epithelium. Nature Physics , 2020.

S. Gsell, E. Loiseau et al., Hydrodynamic model of directional ciliary- beat organization in human airways. Scientific Reports , 2020

Requirements

Research Field

Physics

Education Level

Master Degree or equivalent

Skills/Qualifications

A Master degree in physics (soft matter, biophysics…) or in biomechanical engineering. The selected PhD student must have a keen interest in interdisciplinary project.

Languages

ENGLISH

Internal Application form(s) needed

phd offerMuFlow.pdf

English

(223.99 KB - PDF)

Download

Additional Information Work Location(s)

Number of offers available

1

Company/Institute

Aix Marseille University / CNRS

Country

France

City

Marseille

Street

campus de luminy

Geofield

Where to apply

E-mail

[email protected]

Contact

City

Marseille

Website

https: // www. cinam.univ-mrs.fr/cinam/en/team/physique-et-nano-micro-ingenierie- pour-le-vivant/

Street

Campus de Luminy

STATUS: EXPIRED