Full project description ESR 19

ESR 19: A human gut and -lymphatics on chip to model functional immune surveillance and activation; PhD1: development of immune competent gut on chip model – POSITION FILLED

PhD research

Hosts:

Prof. Dr. Sue Gibbs

Department of Molecular Cell Biology and Immunology

Amsterdam UMC, location VUMC

Prof. Dr. Reina Mebius

Department of Molecular Cell Biology and Immunology

Amsterdam UMC, location VUMC

Duration: 48 months

Background

Lymphatics are important for the regulation of tissue and organ homeostasis, and modulation of the immune response. When impaired, it can lead to edema formation, tissue fibrosis, impaired acute inflammatory reactions and impaired resolution of inflammation. Since abnormal adaptive immune responses  are the underlying trigger of most human diseases that are characterized by chronic inflammation , it is essential to integrate organs with a functioning immune system in models that are representative of human diseases. These models can then be used fordrug discovery, drug safety and drug efficacy testing, in both personalized- and regenerative medicine. These models can then also be used for studying the abnormal adaptive immune responses seen in chronic inflammatory diseases and allow to mimic the effect of the microbiome on disease models..  This project will make use of our expertise in microfluidic devices (organ on chip) and the development of state of the art organotypic immune competent barrier models (skin and mucosa) to develop and test a novel immune competent gut on chip model which will combine with an in parallel developed lymph node on chip in the final year.

This project aims to develop a next generation functional organotypic gut model with integrated lymphatics, lymph nodes and immune cells in an Organ on Chip (OoC) format which is capable of immune surveillance and testing or orally taken RA drugs.

Approach 

The workplan will consist of the following phases:

  1. Development of a 3D organotypic gut model consisting of a differentiated, polarized epithelium on a vascularized fibroblast populated lamina propria with integrated immune cells.
  2. Generation of a full thickness human gut-on-chip with endothelial cells lining the microfluidics compartment which is stable in culture for 4 weeks
  3. Combination of gut and lymph node on a chip by including functional lymphatic drainage flow.
  4. To induce an inflammatory response in the integrated gut-LN OoC

The technology will be designed to be easily adaptable to other healthy and disease organ systems in the future.

Our research team

  • – Dept. of Medical Immunology (location VUmc): Dr. H. Bontkes– Dept. of Medical Oncology (Cancer Center Amsterdam): Prof. dr. T de Grijl 

    – National consortium for human disease model technologies (hDMT), gut on chip theme group (https://www.hdmt.technology/)