MGPS & l'INRA
The microbiota in human health
and well being.

Functional metagenomics - MetaFun

The functional metagenomics approach was born at INRA in 2003 when Hervé Blottière and Joël Doré conceived a new method to study interactions between intestinal bacteria and human cells.

The complexity of the intestinal ecosystem and our inability to culture most of its microorganisms led to the development of this new method based on massive cloning of large DNA fragments from stool microbes in an easily cultivable host, and high throughput screening to decipher the clones' properties.

Exploration of microbes-hosts interactions have led to extended recognition of the role of commensal intestinal microbes in several physiological mechanisms, from epithelial barrier development to immune system development and metabolism as well as neurological aspects.

Nevertheless, in many instances, the molecular mechanisms of host microbes cross-talk have not been addressed and, in most cases, the cross talk molecules remain totally unknown. The functional metagenomics approach allows such explorations independently from phylogenetic identity or cultivability of the microorganisms producing the cross-talk molecules. This opens perspective of discovery of novel signaling molecules relevant for physiological situations and preventive recommendations as well as pathological contexts and therapeutic applications.

Driving scientific discoveries and scientific productions       

Dozens of bioactive clones have been identified and characterized so far, leading to the discovery of new molecules modulating signaling pathways in intestinal epithelial cells. The screening processes have been optimized to provide robust and adaptable SOPs. Besides the metagenomic approach, the platform has been adapted to decipher the impact of commensal and probiotic bacteria on several signaling pathways in human intestinal epithelial cells. [Publications]

Applications for the nutritional and medical fields:

Identification of useful microbial features: anti-inflammatory, anti-proliferative effects, satiogenic properties…

Probiotics (strains selection, mechanisms of action)

Molecules for potential therapeutic applications

Validation of nutritional intervention strategies: nutritional supplements and food providing targeted benefits

Dietary recommendations

Functional foods

Analysis of complex ecosystems of alimentary products

Improved nutritional formulations and microbiological safety

To fulfill its commitments and ambitions towards the academic and industrial communities, Metagenopolis set up the MetaFun platform, and acquired the equipments and developed applications to provide the most performing platform in the field

Metagenomic and large fragment genomic libraries construction: Semi-automatic procedure for preparation of genomic and metagenomic libraries for the exploration of microbe-host interactions by high throughput functional screening

 

Production of new HTS screens: Construction and validation of cellular screens using different reporter systems (luciferase, SEAP, fluorescent proteins) for high throughput identification of clones modulating cellular pathways. Production of new fluorescent cellular screens by knock-in.

 

Automated phenotyping for kinetic monitoring of bacteria-cell interactions and identification of bioactive clones and signal molecules modulating specific cellular pathways.

 

High Content Screening (HCS): High throughput real-time pathway-imaging for the mechanistic description of microbe-host interactions using fluorescent screens.

These facilities, currently under ISO9001 certification preparation for 2016, allow the platform to cover the whole functional metagenomics process from the construction of libraries to the identification of genes of interest.

The automated phenotyping facility has a screening capacity of 200,000 bioactive clones per year.

Collaboration:

As precursors and leaders in the field, researchers in Metafun wish to apply their know-how and expertise in the framework of collaborations with academics and industry. They provide expert advice to design the study, and to projects from the production of large insert genomic and metagenomic libraries and the construction of cellular screens to the functional screenings and their analysis.

Metafun offers also a service of high throughput screening from existing libraries: from the construction of the project to the analysis of the results.

Resources:

2 Hamilton Star for eukaryotic cell screening of reporter gene activity, 2 Hamilton Star+ for culture of bacteria/lysis/filtration, Colony pickers for metagenomic library construction (Qpix 450), flow cytometer (FACS Arial III), High Content Screening (HCS) epifluorescence microscope.

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