Disease-predisposing or resilience-promoting? Decoding the systems biology and behavioural predictors and determinants of the tipping point of stress

• Applicants: Dr. Nils Gassen; Professorin Dr. Marianne Müller
• Subject Area: Biological Psychiatry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544161359

The concept of tipping points is receiving particular attention in the context of climate change: here, abrupt and persistent changes are often the result of a series of slower processes that undermine resilience and push systems past a critical threshold. Surprisingly, the concept of tipping points has been largely neglected in stress research, and the precise determinants that decide about positive or negative consequences of stress remain unclear. PROGRESS will for the first time leverage complementary expertise and cutting-edge methods to close these gaps by pursuing the following objectives: 1) To use stress-free longitudinal and individual monitoring to establish the time course and temporal dynamics of events associated with the tipping point during social stress in both sexes; including refined behavioral and molecular changes, non-invasive assessment of brain connectivity and cardiovascular function 2) To identify and validate predictive signatures for stress resilience and susceptibility in mouse models and humans and 3) To test the hypothesis that actively promoting resilience can shift the tipping point. To achieve our goals, we will leverage the power of already existing, dedicated, deeply phenotyped human resilience and depression cohorts and empower translationally valid animal models with emerging methods for longitudinal assessment of phenotypes across scales. Advanced integrative computational biology, data mining and machine learning algorithms will be applied to integrate molecular, phenotypic and behavioural data, to build explainable models and to enable direct translation to humans. Due to its disruptive potential and long-term perspective, PROGESS will have a sustainable impact on advancing resilience research. In addition to our commitment to scientific excellence, the consortium will provide tailored mentoring to junior researchers to support their academic development. Through scientific exchange, mobility, and networking we aim at educating future leaders in interdisciplinary resilience research. Promoting resilience is a topic of prevention. Accordingly, scientific outreach activities are based on two pillars,1) to achieve the highest possible level of penetration, awareness and education of our research in the general population where stress is overwhelmingly associated with negative aspects and 2) to specifically target at-risk populations. In this way, our European network will actively contribute to change this fundamentally very negative attitude toward stress, and share our findings with those who need them most. Successful completion of the project will enable early prediction of the tipping point and personalized risk stratification. Ultimately, we expect our research to help transform modern psychiatry into a science of prevention.

• DFG Programme: Research Grants
• International Connection: Estonia, Finland, Slovakia, Switzerland
• Cooperation Partners: Professor Johannes Bohakek, Ph.D.; Professorin Iiris Hovatta; Professor Dr. Igor Jurisica; Helena Sork, Ph.D.