Post doctoral position in LIMMS/CNRS-IIS – Developpement of a microfluidic biochip for induced pluripotent stem (iPS) cells differention
Offer type: job
The 2 year postdoctoral fellowship position will be based in the the Institute of Industrial Science of the University of Tokyo, as a collaboration between Eric Leclerc (LIMMS-Japan, organ on chip), Pr. Sakai (Univ. Tokyo, liver tissue engineering, iPS biology) and Pr. Fujii (Univ. Tokyo, applied microfluidic).
The drug-induced hepatotoxicity (or DILI for Drug-Induced Liver Injury) is a worldwide issue
for clinicians, the pharmaceutical industry and regulatory agencies of the drug. The drug hepatotoxicity is the first acute toxicity leading to death or liver transplantation failure. The hepatotoxicity is also the leading cause of attrition of a large number of therapeutic molecules and their withdrawal from the market. This is the reason why it is essential to develop tools to assess the hepatotoxicity of drug candidates as early as possible during their development. Many models exist at present to estimate the toxicity of drugs (animal models, cell lines, primary hepatocytes). But these models exhibit many limitations, as we will describe later. The project iPS on chip aim to develop, from hepatocytes derived from induced pluripotent stem cells (iPS), a microfluidic culture model that will allow a better stable and reproducible differentiation patterns for assessment xenobiotic toxicity.
The context is the regeneration of tissues and the substitution of bioartificial organs, predictive toxicology, 3D tissue engineering, to overcome the deficiencies of the biological systems, are problems using new multi-disciplinary approaches proposed by Pr Fujii and Pr Sakai. In this frame we propose an integrative research procedure, to improve the iPS differentiation using microfluidic devices.
We will need to develop and explore different types of biochips. We will need to optimize the three-dimensional microfluidic biochips suitable for dynamic liver iPS cell culture. For that purpose, BioMEMS recent progress will be implemented in the device conception. It included the consideration of new approach in micro engineering, biomaterials and sensors technology to functionalize the biochips. Then, in this work, we will have to adapt the protocol that allows the cultivation of iPS in the new biochip. To do this, the effects of extracellular matrices, the inoculation density of cells, the co-culture types, the perfusion rates in the biochips, the sequences and doses of additives involved in the differentiation will be tested. We will analyze the pertinence of differentiation in parallel to a Petri. Biological assays to validate the hepatic differentiation will include investigations of mRNA levels analyzed by RTqPCR or microarrays, hepatic biomarkers detection (ALB, AFP), epigenetics analysis and proteomics. For that purpose miniaturization concept and design issues will be important features to allow the best control of endocrine and paracrine factors and the relevant analysis at key time points.
Doctor graduate researcher with skills in liver cell biology, stem cell biology, bio engineering, pharmacology
Please send to limmsadm(at)iis.u-tokyo.ac.jp with email subject LIMMS_PD_2015-1-YOURNAME:
– Curriculum vitae (including education & professional history, publication list, reference(s) and photo)
– Motivation letter to LIMMS, and the Statement of Purposes (your future plan).
– One reference and/or recommendation letter