COSMIC: Combating Disorders of Adaptive Immunity with Systems Medicine
COSMIC is a systems medicine project. Systems medicine has recently emerged as a new concept added to the toolbox of clinical and biomedical researchers to address key questions in complex (immunological) human diseases. It pursues an integrative and holistic approach by involving different sectors, integrating disciplines, and combining experimental and computational approaches to the benefit of patients. We focus on mechanisms of immunological memory and antibody formation as part of the adaptive immune system, and how these are involved in the pathogenesis of B-cell lymphoma (BCL) and rheumatoid arthritis (RA).
The adaptive immune system is a key component of our defence against agents that cause infection or disease and refers to the antigen-specific immune response. This system comprises highly specialised cells and processes, and its humoral component is responsible for memory B-cell formation and high-afﬁnity antibody production resulting from afﬁnity maturation in germinal centres (GC). GCs are specialised anatomical sites typically found in secondary lymphoid tissues where immune cells interact, differentiate and undergo antibody gene alterations. Perturbations of the GC reaction contribute to the emergence of transformed/malignant cells that give rise to BCL, or clones expressing autoreactive antibodies involved in RA pathogenesis. COSMIC focusses on BCL and RA thereby establishing a unique cross-fertilization between the oncology and auto-immunity research fields. Despite recent progress in elucidating molecular and cellular mechanisms involved in the GC reaction, a precise understanding of its dynamics and its role in BCL and RA pathogenesis has yet to emerge. The complexity of the GC will be addressed by the development, application and integration of computational and experimental approaches. COSMIC aims to elucidate the cellular and molecular mechanisms of the GC reaction to understand the development and evolution of BCL and RA. This is expected to lead to the identification of markers that can be exploited for preventive, diagnostic, and/or (personalised) therapeutic purposes to achieve best outcome and leverage the cost-effectiveness of treatment.
COSMIC is a Marie Curie European Training Network funded from the European Union's Horizon 2020 research and innovation programme under grant agreement No 765158.