CE45 - Mathématique, informatique, automatique, traitement du signal pour répondre aux défis de la biologie et de la santé

Multiscale Numerical Simulator of Respiratory Epithelium – SINUMER

Submission summary

The goal of the SINUMER project is to build a numerical simulator to capture the key physical mechanisms of mucus transport in human lungs, and use it to progress on the understanding of severe asthma and Chronic Obstructive Pulmonary Diseases (COPD). These chronic respiratory diseases affect nowadays hundreds of millions of people, and there is still no curative treatment available. Moroever this worldwide burden is constantly growing because of the increase of external toxic agents and pollutants in the air of modern urban societies.

At the roots of these bronchial disorders, lies the bronchial epithelium, where is transported mucus, a complex fluid powered by the coordinated beating of billions of microscopic cilia carried by the epithelial cells. These cilia can synchronize their beating and produce typical waves which transport the mucus through the bronchial tree. This transport is determined by largely unknown physical mechanisms involving a hydrodynamic coupling between the ciliary beats and the surrounding multiphase non-Newtonian fluid.

The numerical environment built in SINUMER will be the first of a kind in respiratory research at this level of realism, taking advatange of an interdisciplinary approach which combines complementary experiences and know-how on mucociliary transport, independently acquired in each discipline, and a synergistic approach linking computational fluid dynamics, biophysical experiments and medicine.
The numerical environment will be used towards two objectives:
-the first one is to better understand the multi-scale biophysical mechanisms involved in the transport of mucus, from the individual cilia beating to their macroscopic collective motion, by unraveling macroscopic laws to link the microscopic scale with the clinical observables. This will allow to elucidate the role of the epithelium parameters: density, frequency, direction, beating patterns and coordination of cilia, and mucus rheology;
- the second one is to provide a numerical diagnosis tool for chronic respiratory diseases, based on the identification of relevant biophysical markers of mucociliary alteration. The prospects are therefore to study in-vitro and in-silico innovative strategies for the development of therapeutic curative and not only symptomatic.

The perspective is thus to enrich the knowledge on chronic airway diseases, their phenotypes and their diagnoses thanks to the new light brought by computational fluid dynamics, and to provide a numerical tool, reliable and efficient for prognostic and therapeutic diagnostic steps in human clinical practice. Such an integrated in-silico approach is strongly expected to yield innovative strategies for curative care of chronic respiratory diseases. Moreover, the longer-term ambition of the SINUMER project is to go towards a patient-personalized physical description of the pathologies which relies on the individualized numerical ‘clearance footprint’ of each patient to progress on the major issue of ‘personalized medicine’. An important outcome of SINUMER for the medical community is to provide in-depth modifications of how chronic respiratory diseases are clinically considered, by resetting the focus on the mucociliary transport.

Project coordination

Julien Favier (Laboratoire de Mécanique, Modélisation et Procédés Propres)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

M2P2 Laboratoire de Mécanique, Modélisation et Procédés Propres

Help of the ANR 273,382 euros
Beginning and duration of the scientific project: September 2018 - 48 Months

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