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FRIMED2-FRIPRO forskerprosjekt, medisin og helse

DUCT chip – Immune studies using a bile duct on a chip

Alternative title: DUCT chip - studier av immunologi med en gallegang-på-en-chip

Awarded: NOK 12.0 mill.

The interaction between the immune system and the environment is believed to be the driving force behind most inflammatory and auto-inflammatory diseases. In this project we will adapt these scientific questions to microfluidics system where pipes and pumps will represent the bile ducts and blood vessels. Through this system we will circulate immune cells to investigate immune processes in the bile ducts. This system will be constructed using mouse cells as well as human cells from patients. This is especially relevant for two important inflammatory diseases affecting the bile ducts, primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). We have access to material from patients with both of these conditions. To be able to use this technology together with patient material we have joined forces from the fields of immunology, developmental biology and stem cells. The project leader and the collaborators are affiliated with a Norwegian center of excellence specifically working on microfluidic systems for studying biology. After developing the system, we will use it to circulate bile and immune cells and investigate how we can modulate inflammation using different pharmacological compounds with the aim of discovering new treatment modalities.

The interaction between the immune system and the environment is believed to be the driving force behind most inflammatory and auto-inflammatory diseases. We will model this inflammatory process in the bile ducts using an organ-on-a-chip (OoC) system with a specific focus on unconventional T-cells represented by mucosal associated invariant T cells (MAIT) and natural killer T (NKT) cells. Inflammation in the bile ducts is the hallmark for two important inflammatory conditions affecting the bile ducts, primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). We have access to biobanked clinical material from patients with both of these conditions. In addition, our laboratory has access to all the relevant mouse models for studying NKT and MAIT biology and mouse models for bile duct inflammation. Specifically, in this project we have joined forces from the fields of immunology, developmental biology and stem cells aiming to use OoC systems to understand bile duct immunology. The project leader and the collaborators are affiliated with the Norwegian center of excellence hybrid technology hub (HTH) that is currently developing a modularized OoC system. We will build on expertise at HTH and develop the DUCT chip modelling the bile ducts. After developing the DUCT chip, we will use microfluidics to circulate bile and immune cells in separate circuits on the chip with a bile duct lined by cholangiocytes from human or murine organoids. This will allow us to uncover biological processes governing antigen presentation in the bile ducts that we will modulate/”treat” by pharmacological agents.

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FRIMED2-FRIPRO forskerprosjekt, medisin og helse