PhD-student: development of immune competent lymph node on chip model including lymph node stromal cells, lymphocytes, and dendritic cells

Amsterdam UMC, location VUMC , Amsterdam, The Netherlands, 08/10/2019

Description

This project is focused on developing an immune competent lymph node on chip for mimicking human adaptive immune responses and the control of these responses by the lymph node stromal cells. This project will combine cutting-edge research on lymph node stromal cells and adaptive immunity with advances in tissue engineering, including organ on chip. This project will work in parallel to, and combine in the final year, with the project aimed at developing organotypic gut on chip.

Research project ESR
PhD research

Hosts:
Prof. Dr. Reina Mebius
Department of Molecular Cell Biology and Immunology
Amsterdam UMC, location VUMC

Prof. Dr. Sue Gibbs
Department of Molecular Cell Biology and Immunology
Amsterdam UMC, location VUMC

Duration: 48 months

Title of the project:
A human lymph node on chip to model the human adaptive immune response within its natural environment created by lymph node stromal cells. PhD2: development of immune competent lymph node on chip model including lymph node stromal cells, lymphocytes, and dendritic cells.  

Background:
Activated innate immune cells migrate via the lymph to the draining lymph nodes. Within these lymph nodes, innate immune cells start the adaptive immune response which is tailored to the injury that has occurred in the tissue and can provide lifelong protection. This adaptive immune response is formed by T- and B-lymphocytes. Within the lymph nodes, mesenchymal stromal cells play an active role in controlling this adaptive immune response. We work under the assumption that when these mesenchymal stromal cells are not functioning properly unwanted adaptive immune responses against self-antigens will occur, ultimately resulting in chronic inflammation as seen in RA. Therefore, in this project we will develop an organotypic 3D lymph node model allowing to better mimic adaptive immune responses. This model can subsequently be used for drug discovery, drug safety and drug efficacy testing, in both personalized- and regenerative medicine. Furthermore, it can be used in combination with gut, skin and lymphatic drainage on a chip. These models can then also be used for studying the abnormal adaptive immune responses seen in chronic inflammatory diseases and ultimately 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).

Aim:
This project aims to develop a next generation functional organotypic lymph node with integrated lymphatics that can drain gut 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. To develop a human HLA-matched 2D tissue culture system of dendritic cells, naive T cells and lymph node stromal cells
  2. To develop HLA-matched 3D organ on a chip lymph node in which naïve T cells, dendritic cells, and lymph node stromal cells are integrated
  3. To combine 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:
– Amsterdam Rheumatology and immunology Center (ARC): Dr. Lisa van Baarsen
– Dept. of Medical Oncology (Cancer Center Amsterdam): Prof. dr. T de Gruijl
– National consortium for human disease model technologies (hDMT) https://www.hdmt.technology/

Your profile:
– You have a Master degree in Biomedical Sciences, with affinity for cell biology,
– You have relevant skills in cell culture and immunological methods
– You have interest in organ on chip and organoid model development

We seek a highly motivated scientist who enjoys an interdisciplinary environment and an interdisciplinary project, able to work independently but also as part of a team.

For information and how to apply: https://www.arcaid-h2020.eu

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