The GUTVIBRATIONS team

GUTVIBRATIONS is a multidisciplinary international consortium that consists of 7 esteemed European partners from the fields of academia and industry. Our academic partners are the Amsterdam UMC (The Netherlands), Technical University of Denmark (Denmark), University of Leuven (Belgium) and KTH Royal Institute of Technology (Sweden). Our industrial partners are UniQure Biopharma BV (The Netherlands), BIOLAMINA AB (Sweden) and STEMCELL Technologies UK ltd. (United Kingdom). Take a look at our partner’s locations and read our commitment to sustainability here.

 

Interested in joining the GUTVIBRATIONS team? Then check out our vacancies and apply!

With its next generation organ-on-chip technology, GUTVIBRATIONS will fast track drug development that will minimise costs, lower disease burden and save lives.

Changing the game in life science research

Organ-on-Chip (OoC) technologies hold promise in accurately mimicking human organs and organ systems in vitro and therefore have great potential to be game-changing in life science research. Over the last decade, several excellent OoCs have been developed such as lung-on-chip, blood-brain barrier (BBB) on chip and skin-on-chip.

 

One of the major obstacles that faces the broader implementation of OoCs is that most of these models are not user-friendly: they are expensive to implement and complex to operate (even more so when connecting multiple organ systems).

To push the OoC technology forward in life science research, GUTVIBRATIONS will develop a next-generation gut-brain axis organ-on-chip that is easy to use.

The gut-brain axis is a bidirectional network that is of significance in maintaining homeostasis. The gut-brain axis has garnered tremendous attention in the last decade and has also been implicated in disease. For instance, intestinal health has a significant impact on brain function and neurodegeneration. Dysregulation along this axis is associated with neurodegenerative diseases and psychiatric disorders. Although the interplay between the gut and its associated microbiome with the brain via the Vagus nerve and the neuroendocrine signalling has been of interest, the gut and brain are also linked via another critical route i.e. the immune system, including vascular and lymphatic systems. The latter routes of interactions are of importance in infectious disease and specifically, for pathogens that enter via the enteric system. For instance, an enteric virus (e.g. poliovirus) after ingestion has to navigate the complexity of the gut mucosa to enter the blood circulation and cross the BBB before inducing brain disease such as acute flaccid paralysis. While model systems are being developed for the gut-brain axis interaction via the Vagus nerve, there is a lack of model systems to study the immune routes of interaction which will be specifically addressed in GUTVIBRATIONS .

While developing the gut-brain axis organ-on-a-chip, GUTVIBRATIONS will focus on the following aspects:

1. Making the OoC accessible and user-friendly

A biological laboratory lacks the expertise and equipment to implement the current OoCs. The end-users should be facilitated with minimal training and without the need for significant investment into equipment and peripherals. In GUTVIBRATIONS, we address this by using a 3D printed multiwell platform called STACKS that is similar to Transwell® inserts, familiar to any laboratory employee, from both academia and industry, and can be operated with just a pipette.

2. Simulating human physiology

GUTVIBRATIONS takes a biologically driven design to create a realistic human microenvironment through the use of human stem cell-derived organoids and organ-specific primary cells combined with a naturally occurring extracellular matrix (ECM) scaffold called Biosilk, a recombinant spider silk protein. The use of stem cells will ensure the recapitulation of the human genomic context while also introducing biological variation observed in humans. The naturally occurring Biosilk ECM will result in an in vivo like microenvironmental niche with high predictive power.

3. Fit-for-purpose and validated

As a demonstrator, the OoCs in GUTVIBRATIONS will be employed for simulating viral-induced human diseases and antiviral drug screening. Immediately after GUTVIBRATIONS, this will be extended for validating the gut-brain axis OoC for other human diseases with significant disease burden.

4. Standardised, robust and reliable

A set of standardised media and protocols will be developed for the different co-culture conditions to ensure that the OoC is robust and reproducible based on defined quality criteria. Besides, all ECM proteins included in the Biosilk will be defined, reducing technical variability.

5. High throughput for industrial applications

The 3D printed platform is currently used in a 12-well plate format which will be scaled up to medium (24-well) and high (96-well) throughput formats. Also, the multiwell plate design ensures automation with pipetting robots which is essential for industrial applications. This will be validated by the demonstrator based on set quality standards to ensure robustness, repeatability, and readiness of the system.

6. Reduce animal testing

Drug development is heavily reliant on the use of cell lines and small animal models such as mice in the preclinical stage. Virology, in particular, needs these models as viruses require a host for replication. However, cell lines and animal models do not reflect the human situation and in most instances, the animal does not mimic human disease correctly. Therefore, having a human-based model evaluating human disease and the related therapeutic outcome will lead to a reduction in the use of ineffective small animal models.

Modular approach

To deliver a biologically-driven gut-brain axis organ-on-chip with a user-friendly design, GUTVIBRATIONS will take a modular approach where modules simulating different regions or functions along the gut-brain axis are separately developed and validated before assembly into the complex gut-brain axis OoC. Each module will comprise of three layers – STACKS, Biosilk, and human organoids.

STACKS

A 3D printed platform similar to Transwell® inserts. STACKS is easy to fabricate, simple to use, readily scalable, and stackable system in the multiwell plate format.

Biosilk

A biomaterial made from recombinant spider silk protein and can be functionalised with ECM proteins such as laminins to create an organ-specific microenvironmental niche.

Organoids

Stem cell-derived models that recapitulate organ function and phenotype. Organoids will be supported by other organ-specific primary cells.

Using this layered design, the following modules will be developed:

 

  • Gut epithelial-mesenchyme model. This model mimics the interactions between the gut epithelium and mesenchyme found in the underlying ECM.
  • Gut epithelial-immune cell model. This mimics the interactions between the gut epithelium and immune cells forming the first line of gastrointestinal defence.
  • Gut mucosa model. This model combines the models from 1) and 2) to create a complete gut-on-chip.
  • BBB model. This model mimics the interactions between the brain endothelium and brain associated cells together forming the protective barrier around the brain.
  • BBB-brain model. This model combines the BBB model in 4) with human brain organoids to recreate a brain-on-chip.

 

Modules 3 and 5 will be combined to form the gut-brain axis OoC.

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