GROWTH – Research and Training in Early Life Nutrition to Prevent Disease
Figure 1 : Overall concept of GROWTH
The interplay between nutrition, gut microbiota, and its large number of metabolic and immune mediators plays an essential role in the development of gut immune homeostasis in early life. This interaction needs to be better understood because a disturbed immune function in the neonatal period is harmful for neonatal survival and enhances the risk of chronic inflammatory disease later in life. Preterm infants have an immature gut and an associated intestinal state of dysbiosis, which limits the efficacy of nutritional interventions to
- support early life nutrition,
- prevent sepsis and conditions such as necrotizing enterocolitis and intestinal failure, an
- reduce the risk of chronic inflammatory diseases mediated by the gut.
A major barrier to elucidating the critical nutritional-host-microbiome interactions and reducing neonatal mortality is the lack of expertise in this rapidly emerging area of metabolomics. The GROWTH consortium is taking a multidisciplinary approach making use of a large-scale pre-existing clinical cohort of neonates, and state of the art analytical and bioinformatics tools. GROWTH is an Innovative Training Network focused on European Industrial Doctorates that aims to train young business-oriented researchers in developing pathological insights, biomarker diagnostics and personalized nutritional interventions for intestinal failure in neonates and preterm infants. Cherry Biotech is one of several non-academic in the life sciences field; collaborating with academic institutions to shorten the path from basic research to clinical applications.
GROWTH : INSIGHT TO THE PROJECT
One main bottleneck in researching the interaction of the host and gut microbiota is culturing anaerobic microbiota together with oxygen dependent gut epithelial cells. This challenge will be addressed here at Cherry.
In detail, we will design and validate a gut-on-a-chip microfluidic system that works for mouse and human epithelial cells by (1) defining the chip specifications based on identified end users and outcomes requirements, (2) test and determine most suited materials, (3) design and prototype the chip, (4) characterize the chip (optically, thermally) and perform quality assurance, and (5) validate the gut-on-a-chip system by testing in wet lab conditions and compare it with 2D and 3D organoid cultures.
With this gut-on-a-chip, Miriam will move to the Academic Medical Centre to investigate AhR ligands and IL-22 in feces of preterm infants in relation to delivery mode and nutrition. Lastly, the mechanisms of action of AhR producing bacteria and AhR ligands will be assessed in gut development using the newly established gut-on-a-chip system. Another researcher from the consortium will join Cherry to further work on chip development and membrane design.
FIELD OF APPLICATIONS
3D CELL ANALYSIS
Innovation using CUBIX
To implement the advanced gut-on-a-chip model systems, the newly developed CUBIX microfluidic perfusion station will be utilised. It is equipped with the fastest and most precise flow control system and temperature control module enabling real time control of accurate micro-environmental parameters, as well as tight gas control mechanisms for oxygen, nitrogen and carbon dioxide. With the fastest microfluidic flow switch matrices (2,400 switches/minute), this system will also enable to mimic peristalsis shear stimulus of the gut. The perfusion system will allow the addition of fungi and microbiota to the newly developed gut-on-a-chip culture in order to follow the interactions between the epithelium and the added organisms during live imaging experiments. This project will lead to the development of the first platform capable of precise control of 3 critical parameters of the culture (temperature, flowrate and gas concentrations) in an organ-on-a-chip device.
Spreading the message
The GROWTH consortium, funded by the European Commission (2019-2023), is training a new generation of researchers working on new pathological insights, biomarker diagnostics and personalized nutritional interventions for intestinal failure in neonates and preterm infants. Academic and industry partners, covering various disciplines ranging from fundamental research to clinical paediatrics and analytical chemistry to organoid and gut-on-chip applications, have teamed up:
- Gut Research BV (The Netherlands)
- University Hospital Bonn (Germany)
- Imperial College London (United Kingdom)
- Academic Medical Center (The Netherlands)
- Cherry Biotech (France)
- VU Medical Center (The Netherlands)
- TNO Research (The Netherlands)
- Radboud University Medical Center (The Netherlands)
GROWTH is a European Industrial Doctorate programme that requires PhD students to spend at least 50% of their time (18 months) in the non-academic sector.
GROWTH website url: http://www.growth-horizon2020.eu/
Figure 2: GROWTH involves a multidisciplinaryapproachon the relation betweennutritionalmetabolomicsand intestinal inflammatorydisease. Highlycomplementarycompanies(blueboxes) and academicinstitutes (yellow boxes) are connected with expertise in the fields of (paediatric) gastroenterologyand surgery, immunology, nutrition science, analyticaltechnology, metabolomics, bioinformatics, organ-on-a-chip model systemsand microbiotaand mycobiotasequencing.
The project manager: Miriam GRAUTE
Miriam Graute is a Marie Curie ITN/EID Early Stage Researcher, focusing on the host-microbiome interaction in the infant gastrointestinal tract
Dr. ANTONI HOMS CORBERA CTO
(CHIEF TECHNOLOGY OFFICER)
Dr. PIERRE GAUDRIAULT
This project has received funding from H2020-MSCA-ITN – program under grant agreement No. 814168
Disclaimer: this content reflects only the author’s view and the EU Agency is not responsible for the information it contains.