Background, aims, hypotheses, and research structure

Understanding living organisms in the context of coordinated gene and molecular function and translation of this knowledge into better human health is a great challenge and one of the central aims of medical systems biology. The immune system responds to genetic and biochemical variations in an adaptive manner that may, however, contribute to autoimmune disease. The immune system plays an important role in many other diseases, but the interplay of the immune system and other physiological systems is poorly understood.

The overall objective of this CoE is to understand the molecular mechanisms that control the immune system as well as the interactions between the immune system and other physiological systems in health and disease, and to translate this knowledge into novel treatment and prevention strategies of inflammatory/immune-mediated disorders, with specific focus on type 1 diabetes (T1D).

Based on our preliminary findings, the key hypotheses that will guide our research are that

1. T1D and several other inflammatory diseases result from physiological adaptation triggered by metabolic stress, and the subsequent disease in some individuals is due to defective regulation of the immune response (e.g., its amplitude or timing);

2. A better understanding of signaling and transcriptional regulation of T-cell differentiation as well as the relationship between the circulating metabolome, T-cell metabolome, and ultimately T-cell function in the context of T1D will provide important new insights into the role of metabolism in immune regulation in health and disease, which in turn will ultimately lead to new immunomodulatory therapeutic avenues.

Reflecting the highly interdisciplinary composition of this CoE, the research will be divided into four research lines including

1. clinical research (PIs: Mikael Knip, Jorma Toppari);
2. biomarkers and metabolome research (PI: Matej Orešič);
3. molecular systems immunology (PI: Riitta Lahesmaa);
4. computational systems biology (PI: Harri Lähdesmäki).

Valuable and unique clinical resources such as the Finnish Type 1 Diabetes Prediction and Prevention study (DIPP) will be integrated with state-of-the-art systems biology and immunology and cutting-edge research infrastructure, potentially leading to novel discoveries of early causes of disease and to hypotheses which can be tested with mechanistic studies, and ultimately, to novel solutions for prevention or treatment of disease.