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PD fellowship of JSPS on "Development of mathematical model of liver disorders in the frame of metabolic syndrome using human organ on chip based in vitro experiments"

ABG-107058 Emploi Junior
08/08/2022 Autre type de contrat > 35 et < 45 K€ brut annuel
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LIMMS
Tokyo - Japon
Informatique
  • Biologie
disease model, liver, in silico methods, organ on chip, predictive biology
07/10/2022
Recherche et Développement

Employeur

LIMMS/CNRS-IIS IRL 2820 (Laboratory for Integrated Micro Mechatronic Systems) is an international laboratory between the French CNRS (Centre National de la Recherche Scientifique) and Institute of Industrial Science (IIS), The University of Tokyo, located in Komaba, Tokyo. LIMMS has more than 27 years of experience in international cooperative research and has welcomed more than 300 researchers from France and Europe.

 

LIMMS opens a new postdoctoral position in the laboratory of the Professors Sakai and Nishikawa, Institute of Industrial Science, University of Tokyo, collaboration with Eric Leclerc (CNRS Director, Visiting Researcher at UTokyo) and Mathieu Danoy (Assistant Professor), LIMMS/CNRS-IIS (UMI 2820). The recruited researcher will be located at the Sakai/Nishikawa laboratory located at the Hongo Campus of the University of Tokyo.

 

Poste et missions

  The scientific challenge is to identify the mechanisms of the development of the human metabolic syndrome. Metabolic syndrome refers to a complex disorder involving several tissues and organs (such as liver, pancreas, adipocytes, heart) and their interactions possibly resulting in diabetes, obesity, non-alcoholic fatty liver disorder (NAFLD) and ultimately in liver fibrosis, blood vessel disorders, cardiac failure. The state of art of metabolic syndrome has documented the organ cross talks in a few papers based on “classical” 2D culture and mainly in animal models. Although food was identified as one source, the sequence of the development of the disease is still controversial. The systemic complications and the lack of pertinent human model leads to bottlenecks in risk evaluations, diagnosis, therapy and thus to industries and clinical demands.

 

 Because metabolic syndrome is systemic disease, the technological challenges are to consider the interactions between the different organs. To solve this problem, we propose a strategy to couple an organ on chip in vitro approach coupled with an in-silico methods to reproduce the organ-to-organ communication.

 

 In this particular JSPS post-doctoral project we aim at building the mathematical Agent population-Based Model (ABM) of the liver biochip because liver is the central organ of several metabolic disorders. The first stage of the project will consist to build a mathematical model from a pre-existing system biology liver fibrosis model (based from Adverse Outcome Pathways, literature) that the candidate will have to modify to suit for biochip. Then in a second stage, it is expected to extend the model to simulate NAFLD. The experimental data to calibrate the system biology models (from in vitro liver organ on chip) were already established from other lab team members (proteins, genes and metabolites data sets for healthy liver, liver fibrosis were already generated) or extracted from literatures. The third step, we wish to investigate how the liver disorder progress from early steatosis up to fibrosis and how this progression is modulated by the organ on chip configuration. Thanks to the ABM model we wish to investigate the effects of the biochip zonation, cell density, type of cell cocultures, dynamic microfluidic cultures, nutrients local concentrations, cytokines’ accumulation. Ultimately, we wish to confirm how the organ on chip data can be used to feed mathematical models in order to extrapolate the prediction to human disorders.

 

 Regarding the mathematical methods, we have interest to agent population-based model (ABM) because the multicellular levels of the pathology development. As alternative and back solutions, we are open to the candidate suggestions related to mathematical integration with several numerical framework such as the Physiological based pharmacokinetic modeling (PBPK model) coupled with system biology models, the Dynamic Energy Budget (DEB) models (as far as we work with stem cells) that can help to solve our problems using in-silico methods.

 

Fellowship periods and periods for arrival in Japan:

Two years starting between April 1st and September 30, 2023

 

Rewards:

Paid equivalent to the JSPS Postdoctoral position

Mobilité géographique :

Internationale

Télétravail :

Occasionnel

Profil

Skills:  

Candidates are expected to have a background of computational biology and mathematical modelling. The candidates should have interests in pharmaceutical science and biological science. Skills in disease modeling and Agent Based Model will be helpful. A challenging sprit would help a lot for tackling the interdisciplinary and cutting-edge research area of the project.

Objectifs

Goals:

 

The prospective postdoctoral researcher should establish a stable liver mathematical model based on the biochip technology and apply it for the hepatic fibrosis. Proposition to extend the model to NALFD is also expected. The researcher should understand the concept of the technology and learn from the experimental details (such as the key parameter of the cell culture on chip) to be able to integrate them in the mathematical model. Then, the candidate is supposed to propose a framework in which we can in the future extend the model by including another organs involved in the metabolic syndrome. Ideally, we would like to investigate integration and crosstalk with pancreas tissues. Finally, the researcher will start a more systematic work on the dependence of the liver disease development based on the human physio pathological situation.

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