SCIENTIFIC CHALLENGES
NOCI involves three Scientific Challenges:
Mastering human stem cell and organoid biology in complex multicellular structures for organ-on-chip formats (S1)
Scientific Challenge S1: mastering human stem cell and organoid biology in complex multicellular structures for organ-on-chip formats
Ten-year goal: To understand how cell-cell interactions and tissue-microbiome interactions affect tissue function
and to explore what the biomedical relevance is of the changes in tissue function that are brought about by
complex, multicellular interactions.
Coordinating scientists: C. Wijmenga (UMCG) and H. Clevers (HI/UMCU)
Collaborating partners: M. Netea (RU), M. v/d Wetering, J. Drost (HI/UMCU/PMC), A. Zhernakova, J. Fu (UMCG)
Mastering biomarker resolution in monitoring disease (S2)
Scientific Challenge S2: Understanding health and disease: how fluid flow, inflammation and mechanical force affect tissue (patho)physiology, mediate systemic effects, and reveal biomarkers for monitoring disease
Ten-year goal: To further understand how mechanical force and inflammation affects tissue function in health and disease, identify markers that reflect these responses and determine how this can be measured quantitatively
Coordinating scientists: A. van den Berg (UT) and C.L. Mummery (LUMC/UT)
Collaborating partners: A. van der Meer, K. Broersen, L. Segerink (UT), V. Orlova, M. Goumans, R. Davis (LUMC),
R. Passier (UT/LUMC), E. van Rooij (HI/UMCU), B. van de Water (LU/LACDR), R. Janssen (Galapagos), M. Netea, (Radboudumc), Y. Li (UMCG)
Mastering non-invasive methods to monitor signal transduction, gene expression and epigenetic regulation over time under different (patho)physiological conditions (S3)
Scientific Challenge S3: Understanding complex signals in multicellular tissues and mastering noninvasive methods to monitor signal transduction, gene expression and epigenetic regulation under (patho)physiological conditions.
Ten-year goal: To understand how cell signals are affected when cultured in complex tissue architectures through real-time sensing and processing. Biochemical, electrophysiological and biomechanical interactions within tissues are of great importance in understanding states of health and disease. Organ-on-chip technology will reveal how complex geometries, soluble gradients and mechanical forces affect tissue function.
Coordinating scientists: L. Sarro (TUD) and M. Ferrari (LUMC)
Collaborating partners: S. Kushner, Y. Elgersma, J. Gribnau, A. Maassen van den Brink (Erasmus MC), G. Terwindt, A. v/d Maagdenberg, S. Van Maarel (LUMC), M. Dogterom (TUD)
Each challenge focuses on fundamental questions regarding cells, disease pathology, its confounders, and materials and formats of microfluidic devices that capture the biomechanics, biochemistry and molecular biology of the tissue niche.
This multidisciplinary approach will result in better understanding of human tissue biology and disease, communication between tissue cells, blood vessels,(body) fluids and component cytokines and hormones, biomaterials and the microbiome, and the effects of genetic variants and mutations.
The resulting knowledge, experimental tools and disease models will be integrated into three Technological Challenges covering the organ-on-chip process
Vision
- make realistic, multicellular and three-dimensional organ-on-chip models of any person each with its unique genetic background, of any tissue of the adult body (minimally the gut, heart and regions of the brain) and that these show normal hormonal and cytokine responses and expected disease features.
- measure how cells and tissues in these models function in health and disease and interact with exogenous factors, capturing genetic and epigenetic and environment interactions and individual cellular and molecular responses.
- understand disease predisposition and progression, and identify factors that can prevent or revert the phenotype
- discover new targets for novel treatments and biomarkers and metabolites for disease diagnosis and monitoring disease onset, progression and therapeutic response.
- predict disease predisposition and severity, which individuals will develop the disease and which microbes exacerbate or reduce the disease state.
- construct multicellular mass-produced chips, which can be linked to mimic communication between organs through metabolites or other cytokines produced, and body-on-chip devices are feasible.
