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HEDoctoral network2023–2027

TOP-GUT · Training for Organoids modelling Physiology and Pathology in the human gastrointestinal tract

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-11-01 → 2027-10-31
EU contribution
€2,718,490
Participants
23
Scheme
HORIZON-TMA-MSCA-DN

Lines connect the coordinator with its partners.

Results in brief

Training for Organoids modelling Physiology and Pathology in the human gastrointestinal tract

The gastrointestinal system (GI) is a major barrier in our body that protects us from, but also interacts with, environmental cues. Every day we introduce several kilograms of food and liquid to our body, and with that bacteria, viruses and toxins. A failure in equilibrium can result in infection and cancer. The study of the GI tract has relied on cancer cell lines or animal models, but these fail to accurately mimic human physiology and offer poor predictive value. This is a general concern in current drug development, as fewer than 1 out of 10 drugs enter the market after showing effectiveness in traditional models. For these reasons, together with a rising societal interest in animal welfare and ethical awareness, the European Union encourages the development of alternatives to animal models to address gaps in the pipeline where such models are lacking or ineffective. The last decade has witnessed a leap forward in the development of new human model systems, driven by breakthroughs in stem cell biology and perfusable organ-on-chip (OoC) technologies. A small biopsy of healthy or tumor tissue can now be embedded in a biological matrix in a plastic plate and grown in vitro, forming a ´´mini-organ´´ known as organoid. While healthy patient-derived organoids (PDOs) recapitulate key organ functions, cancer PDOs reproduce patient-specific pathologies and help predict individual responses to cancer therapies. PDOs can be integrated into OoC platforms to mimic the GI tract flow and to combine different organoids. Within TOP-GUT, we aim to train the next generation of scientist to understand and build model complexity, address future applications for personalized medicine, and manage ethical, regulatory and legal aspects, as well as effective science communication.

Data: CORDIS, © European Union

Project objective

In the aging society, disease burden, such as degenerative diseases and cancer are rising while drug development successes are limited, due to high drug failure rates in the transition from animal experimentation to human patients. This demands re-thinking of the currently used models. Advances in stem cell biology and microfluidics have created new human organ models. These models are neither fully understood, nor fully mimicking the complexity of the tissue. With this new ability to build human stem cell-based models, we have a responsibility to drive these models to implementation – aiming to replace animal experimentation and provide next generation patient avatars for precision medicine. TOP-GUT combines cutting-edge basic and translational science with an outstanding program of education to unleash the full potential of new human organ models, specifically patient-derived organoids and organ-on-chip devices. TOP-GUT will focus on the gastrointestinal (GI) tract, which is the bodies second largest interface with the environment. It is medically highly relevant not only as a major site of cancer development, as target of infectious agents, and as site of inflammatory diseases, but also as one of the major organs for drug uptake and relevance in toxicology. TOP-GUT aims to significantly contribute to our understanding of the current GI models, establish new tools and protocols for more complex GI models, and advance the use of GI models for personalised medicine. In addition, TOP-GUT will address ethical and legal issues to foster acceptance and implementation of the GI models. TOP-GUT will build a solid European network to cooperate, standardize and push GI models into applications, bringing together academia and industry. Together, TOP-GUT educates the next generation of researchers to become new leaders in the field and to drive the implementation of new stem cell based human models to replace animal experimentation in academia and industry.

Original text from CORDIS.

Participants

  • TECHNISCHE UNIVERSITAT BERLIN · BerlinCoordinatorGermany
  • AZAR Innovations · EindhovenNetherlands
  • BAC3GEL, LDA. · Porto SalvoPortugal
  • BAYER AKTIENGESELLSCHAFT · LeverkusenGermany
  • BIONEER A/S · HoersholmDenmark
  • CHARITE - UNIVERSITAETSMEDIZIN BERLIN · BerlinGermany
  • F. HOFFMANN-LA ROCHE AG · BaselSwitzerland
  • FONDAZIONE PER L'ISTITUTO DI RICERCA IN BIOMEDICINA · BellinzonaSwitzerland
  • HELSEDIREKTORATET · OsloNorway
  • HS-Analysis GmbH · Eggenstein-LeopoldshafenGermany
  • I3S - INSTITUTO DE INVESTIGACAO E INOVACAO EM SAUDE DA UNIVERSIDADE DO PORTO · PortoPortugal
  • INNOVATION ACTA SRL · SIENAItaly
  • KOBENHAVNS UNIVERSITET · KOBENHAVNDenmark
  • MIMETAS BV · LeidenNetherlands
  • NOVOZYMES A/S · BagsvaerdDenmark
  • ORGANOBALANCE GmbH · BerlinGermany
  • ROCHE GLYCART AG · SchlierenSwitzerland
  • TISSUSE GMBH · BerlinGermany
  • UNIVERSIDADE DO PORTO · PortoPortugal
  • UNIVERSITA DELLA SVIZZERA ITALIANA · LuganoSwitzerland
  • UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtNetherlands
  • UNIVERSITEIT UTRECHT · UtrechtNetherlands
  • UNIVERSITETET I OSLO · OsloNorway

Links

Data: CORDIS, © European Union