Development of a Gut-on-a-Chip model in a 3D microfluidic platform (OrganoPlate™)
Drug toxicity, and lack of efficacy, remain major issues in drug discovery today and stress the need for better predictive in vitro models. Most drugs are applied orally and will be absorbed into the body via the gastrointestinal tract. In this project a gut-on-a-chip model is developped within a 3D high throughput screening platform, the OrganoPlate™ 1. Mimetas’ PhaseGuide technology for passive liquid handling allows patterning of cells in an extracellular matrix along perfused medium channels. The stratified co-culture options of the microfluidic design will be used to set up a miniature gut organ. This gut-on-a-chip model will be further engineered through CRISPR technology to mimick diseases like Crohn’s disease and Ulcerative colitis to serve as a screening platform for new medications.
The aims of this project are 1.) to establish a gut on a chip model by creating a fully lined and controlled polarized intestinal epithelium with separated apical and basal access in a stratified co-culture with immune cells, 2) to improve and further develop data point density and microfluidics design and to develop gradient capabilities on a microfluidic platform for polarized barrier formation. 3.) to show compatibility of this gut model with high throughput screening techniques (together with Galapagos) , 4.) to develop knock out cell lines of Crohn´s disease mutations and create a 3D gut on a chip model susceptible to Crohn´s disease.
MIMIC is a collaboration between Mimetas B.V. (Leiden), Galapagos (Leiden) and the University of Sheffield. The ESR will be trained at all three locations and enrolled in the PhD programme of the University of Sheffield.
TECHNIQUES: 3D cell culture, CRIPR technology, (fluorescent) imaging and analysis (confocal), PhaseGuide technology, microfluidic design, high throughput screening.
To this position applies a mobility rule. The respective candidate must not have worked for more than 12 months in the Netherlands within the last three years. The candidate needs to be in his/her first four years of his/her research career. The four years are counted from the date a degree was obtained which formally entitles to embark on a doctorate in the country either in the country in which the degree was obtained or in the country in which the research training is provided
•Starting date: 01.01.2016 (or later)
•Duration: 36 months
•Salary: According to the Marie Curie-ITN rules
1.Trietsch SJ, Israels GD, Joore J, Hankemeier T, Vulto P. 2013 Microfluidic titer plate for stratified 3D cell culture. Lab on a chip 13, 3548-54