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Reference : UMR5588-CHAMIS-005
Workplace : ST MARTIN D HERES
Date of publication : Thursday, September 10, 2020
Scientific Responsible name : MISBAH Chaouqi
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 November 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Cardiovascular dysfunctions are the world's leading cause of mortality. Elucidating the biochemical and mechanical factors of blood flow regulation is a challenging issue due to the subtle mechanical and biochemical interplay between the red blood cells (RBC) and the endothelial cells (EC) that form the innermost layer of the blood vessel. EC translate shear stress and ATP (adenosine triphosphate) changes into plasma calcium (Ca) waves. Ca plays a pivotal role in the endothelial nitric oxide (NO) pathway involved in vasomotor control (blood flow regulation).
The motivation behind this project is based on the fact that, despite a huge number of biomedical experiments in the last few decades, the precise pathways of blood flow regulation have not yet been determined. The goal is to develop large scale simulations (using Lattice Boltzmann Methods) taking into account RBC-EC and biochemical signaling to identify and discriminate between various signaling pathways, and to combine them with deep learning and artificial intelligence strategies. This will open the door to future simulations of a predictive nature with potential consequences for diagnosis and therapeutic treatment.
Several fundamental challenges have to be overcome: (i) coping with the multi-level interactions in multicellular architectures and their effect on collective cell dynamic behavior and biochemical signaling, (ii) coupling biochemicals to RBC and EC is a complex, free-boundary, nonlocal and nonlinear problem, (iii) identifying the relevant degrees of freedom for an effective, reduced biochemical model is not an easy task. This work will benefit from close collaboration with experiments on a microvasculature-on-a-chip recently developed in our team. This project is an extension of that by a previous Phd (Hengdi Zhang). Below is a set of preliminary simulations obtained by him. This work may give rise to a Phd (see Fig.1 preliminary simulation).
We will address the following by Lattice Boltzmann simulation (LBM):
• Modelling and simulation of ATP generation and uptake by EC
• Analysis of how a RBC suspension will affect ATP generation by EC
• Analysis of the EC response in complex vascular networks, extracted from medical images (see preliminary simulation in Fig.1)
• Analysis increase of disease (RBC clot formation, etc..)
• Analysis of ATP release and calcium waves under healthy conditions. These experiments will guide the modeling of the interplay between RBC and ATP kinetics in the presence of EC.
• Real blood flow simulations will be progressively substituted by deep machine learning, based on artificial intelligence for the benefit of a huge acceleration.
-Work in a team with regular interactions with Phd's and Postdocs
-Interact with experiments
-Interact with interdisciplinary environment
Constraints and risks
no specific comment
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