Development of a microfluidics-based dynamic gut model to study human microbiome interactions

SCHEME: INTER Mobility

CALL: 2014

DOMAIN: BM - Regenerative Medicine in Age-related Diseases

FIRST NAME: Pranjul

LAST NAME: Shah

INDUSTRY PARTNERSHIP / PPP: No

INDUSTRY / PPP PARTNER:

HOST INSTITUTION: University of Luxembourg

KEYWORDS: Human-microbial co-culture modelHuman Gastrointestinal tract modelHost-Pathogen interactionMicroengineeringMicrofluidicsIntegrated analytical systemsHuman microbiome research

START: 2014-05-01

END: 2014-10-31

WEBSITE: https://www.uni.lu

Submitted Abstract

Mixed microbial communities play pivotal roles in governing human health and disease. Recent large-scale metagenomic sequencing efforts have convincingly corroborated the notion that humans should be considered as superorganisms in which imbalances in microbial community structure and function (dysbiosis), in particular in the gastrointestinal tract, can lead to disease. Although large-scale “meta-omic” studies are greatly advancing our knowledge of the human microbiome, cross-sectional, case-control and longitudinal studies may not have the necessary statistical power to allow causation to be inferred from patterns of association between variables due to the nascent complexity and heterogeneity. Therefore, there exists a distinct need for an in vitro model of the gastrointestinal tract in which emergent hypotheses related to human-microbe interactions and further pathogenesis of the linked diseases can be tested. To fill this gap, we have spent the last two years developing a microfluidics-based co-culture device allowing partitioned but proximal [~500µm] co-culture of human and microbial cells while at the same time allowing molecular interactions between both contingents across semi-permeable membranes [Shah et al, in preparation]. The HuMiX model is an ideal tool to investigate the role of human microbiome interactions in the pathogenesis of idiopathic diseases hypothesized to have roots in a dysbiotic gut. Compatibility to high-resolution omic analyses enables a molecular level snapshot of the host-pathogen interactions holding the key to understand the complex disease mechanisms.This project aims to maximize the potential of the state-of-the-art tools developed during the concluding FNR CORE (HuMiX – C11/BM/1186762) project. The main goal of the present project is therefore to expand the HuMiX co-culture device into a model of the entire human gastrointestinal tract (fluidGUT). The design and model of the fluidGUT model are already drafted but the applicant still needs to simulate, fabricate, test and optimize the flow profiles and fluid retention times on the fluidGUT model. Another additional feature of fluidGUT model is inclusion of magnetically actuated micro-impellers for luminal microbiota reactors, which needs to be miniaturized, integrated, characterized and further optimized for a microscale bioreactor. Prof. Zenhausern’s lab (University of Arizona, USA) has over 10 years of experience in developing miniaturized integrated analysis platforms and this will be crucial for the success of the project and an important learning experience for the applicant. LCSB and Luxembourg currently does not have a microfabrication lab where the applicant can undertake the proposed project. Dr. Zenhausern is an already existing partner on the concluding HuMiX project. Hence it is absolutely pertinent for the continuation of the HuMiX approach and successful implementation of the fluidGUT project, that the applicant builds upon the strengths of the existing partnership where the applicant can be rapidly integrated and get a headstart. Apart from development of fluidGUT model, the applicant is also aiming to increase the throughput of HuMiX model by development of a HuMiX-HT allowing parallel co-culture experiments.

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