Doctoral school : ED 71 « Sciences pour l’Ingénieur » - UTC

Université de technologie de Compiègne – Thesis proposal

Part 1: Scientific sheet

Thesis proposal title Modulating mechanical and biological parameters to investigate phenotypic changes in human liver sinusoidal endothelial cells

PhD grant Doctoral work contract based on a Ministry of Research Grant

Research laboratory unité de recherche : BMBI research team: CBB/IFSB/C2MUST web site: https://bmbi.utc.fr

Thesis supervisor(s) M Vayssade (HDR) ; A Le Goff ; K El Kirat (HDR)

Scientific domain(s) Biology, biomedical and health sciences

Research work The BMBI laboratory aims to develop a relevant bioartificial liver, built with all the liver cell types maintained in a controlled biomechanical environment. Such biological device represents a promising alternative in supplying patients with liver failure. Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells representing the interface between blood cells on one side and hepatocytes and hepatic stellate cells on the other side. In a normal liver, LSECs represent 15 to 20% of liver cells and are exposed to various mechanical constraints (very weak stiffness of the basement membrane, shear stress). Liver endothelial cells also have a discontinuous architecture (fusion of the luminal and abluminal plasma membrane) in areas called “fenestrae”. The loss of the specific phenotype of LSECs (disappearance of the fenestrae, development of the basement membrane, appearance of specific markers) is called capillarization and is an early event in chronic liver injury (fibrogenesis, cirrhosis, hepatocellular carcinoma). In this interdisciplinary project, the PhD student will investigate the role of mechanical and biological parameters on the phenotype of LSECs cultured in vitro. Briefly, gelatin/collagen surfaces with different degrees of stiffness will be used for the LSECs culture. Hydrogels will then be adapted into microfluidic systems for dynamic LSEC culture and controlled shear stress exposition. The secretome effect of normal or cancerous hepatocytes will also be assessed on the phenotype of LSECs. The identification of the parameter(s) modulating the LSEC phenotype and functions would represent a strong progress in the development of a biomimetic/bioinspired bioartificial liver.

Key words Tissue engineering, liver capillarization, mechanobiology

Requirements Skills in cell culture and mechanical characterization of cell culture surfaces. Ability to work in a multi-disciplinary group.

Starting time October 2018

Location BMBI lab, Compiègne

Doctoral school : ED 71 « Sciences pour l’Ingénieur » - UTC

Part 2: Job description

Duration 36 months

Additional missions available Teaching at UTC possible

Research laboratory Biomechanics and Bioengineering, tissue engineering

Material resources Computer, desk Cell culture rooms (BSL 2), cell phenotype characterization (ESEM, confocal microscopy, flow cytometry), nanobiomechanics and nanoengineering (AFM, Q-CMD), microfluidic platform

Human resources 25 permanent researchers, 11 technical and administrative staff, 30 PhD, 10 post-doc + associated researchers

Financial resources BMBI + Ligue contre le Cancer (submitted) Working conditions Monthly meetings with the thesis supervisors.

Research project BMBI, + Ligue contre le Cancer (submitted) National collaborations Institut Pasteur Lille

International collaborations LIMMS (Tokyo univ) (AAP RISE)

International cosupervision (cotutelle)

No

Contact Muriel.vayssade@utc.fr Anne.le-goff@utc.fr Karim.el-kirat-chatel@utc.fr

Please contact first the thesis supervisor before applying online on https://webapplis.utc.fr/admissions/doctorants/accueil.jsf