Female Resilience on-chip

Research on dynamic resilience has so far been solely possible in observational clinical settings (e.g. monitoring of blood pressure, heart rate, mood) and in strongly simplified in vitro assays. To investigate mechanisms that control and alter resilience as well as to describe and validate associated biomarkers, advanced in vitro models that can be subjected to stressors in defined ways and without ethical concerns are urgently required. So far, in vitro models are rarely used because inter-tissue communication, energy homeostasis and basal inflammatory states – essential features of immunometabolism and fitness – are lacking in those models. Organ-on-Chip (OoC) technology enables connection of multiple tissue models, integration of immune components (i.e. pro-/anti-inflammatory cytokines and tissue-resident/circulating immune cells), and the controlled addition of dissolved factors and stressors. In this project, we bring together experts in OoC platform design, organoid development, immunology, genomics, bioinformatics/artificial intelligence, and clinical research to develop a resilience on-chip platform.

We hypothesize that dynamic resilience mechanisms are centrally impacted by metabolic changes during aging that create an overall inflammatory environment which leads to loss of resilience and hence are of immune metabolic nature. To explore this hypothesis with high granularity, we will leverage a three-organ Multi-Organ-Chip (MOoC) connecting hormone, metabolic and immune sensitive organs (WAT, liver and lymphoid tissue), apply a series of readouts that allow the dynamic monitoring of immune metabolic changes in an integrated approach, interrogate the platform with a battery of stressors, and benchmark the in vitro data set with the human in vivo situation on a patient-specific level.

Partner

Wellcome Sanger Institute

University of Oslo