COSMIC Mission

COSMIC delivers the next generation of systems medicine professionals who successfully combat complex human disorders. We will focus on B-cell lymphoma and rheumatoid arthritis, diseases that originate from abnormal functioning of the adaptive immune system, in particular the germinal center. COSMIC develops and integrates experimental and computational approaches, and establish a unique cross-fertilization between oncology and auto-immunity. 
 
Download: COSMIC Summary
 
  • COSMIC in numbers

    10 Beneficiaries
    7 Partner Organisations
    14 Early Stage Researchers (ESRs)
        -13 PhD students
        -1 Industrial researcher
    5 Companies
    9 European countries
        -NL, FR, SE, UK, IT, ES, DE, CH, EL
    5 Visiting Scientists
    4 External Trainers
    5 Members of External Advisory Board
    1 Ethics Advisor
  • COSMIC Research Background

    Systems Medicine

    One of the key question in systems biology is how biological systems (e.g., cells, molecular networks, germinal center) operate upon interaction with their external environment. Answering this question will generate knowledge about the dy­namics of complex systems and quantitative and explanatory computer models based on ex­perimental data.

    Systems medicine implements systems biology approaches in medical research and practice. This involves iterative and reciprocal feedback between clinical investigations and practice with computational, statistical and mathematical multiscale analysis and modelling of pathogenetic mechanisms, disease progression and remission, treatment responses, and adverse events as well as disease prevention at the individual patient level.

    Systems medicine aims at a measurable improvement of patient health through systems-based approaches and practice.

    Source: CASyM
    See also: EASyM
    Further reading: Schmitz, U., and Wolkenhauer, O. eds. (2016). Systems Medicine (New York: Springer)

    Adaptive immunity
    Germinal Center
    B-cell lymphoma
    Rheumatoid Arthritis
    Computational modelling
  • COSMIC Systems Medicine

    Through collaboration with existing systems medicine initiatives (e.g. EASyM, ISBE) COSMIC researchers contribute to systems medicine infrastructure and best practices that reduce time and costs to address clinical needs.

    At the same time this will promote Europe’s position in the health domain.
  • COSMIC Training

    An important aim of the Marie Sklodowska-Curie Action European Training Network (ETN) is to train young researchers (Early Stage Researchers, ESRs) with multi-disciplinary and multi-sectorial scientific and transferable skills required in systems medicine and translational medicine (WP2).

    COSMIC delivers 14 highly skilled systems medicine professionals who are able to address and solve complex clinical questions and to shape the next generation of systems medicine scientists.

 

COSMIC Research programme

Overall Aim

Considering the close relationship between B-cell lymphoma (BCL) and rheumatoid arthritis (RA), and their link to the germinal center (GC) reaction, COSMIC facilitates a unique cross-fertilisation of RA auto-immunity and B-cell oncology research and clinical questions. We aim at providing novel insights into the underlying GC-related, possibly shared, molecular and cellular mechanism(s) of these two diseases. 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.

 

Background

Immune-related diseases such as BCL and RA 

  1. An incomplete understanding of the underlying molecular/cellular mechanisms;
  2. Uncertain diagnosis/prognosis
  3. Variable treatment efficacies of existing drugs.

This results in suboptimal patient management and a huge cost burden on healthcare systems, and prompts for personalized medicine. COSMIC addresses these challenges by pursuing a systems medicine approach focussing on the role of the germinal centre in B-cell lymphoma and rheumatoid arthritis

 

Germinal Center

The adaptive immune system is a key component of our defence against pathogens and comprises highly specialised cells and processes. Its humoral component is responsible for memory B-cell formation and high-affinity antibody production resulting from affinity maturation in germinal centres (GC), specialised anatomical sites typically found in secondary lymphoid tissues such as lymph nodes or spleen. B-cell clones express a unique B-cell receptor (BCR) consisting of an immunoglobulin (IG) whose variable domain is encoded by a rearrangement of the IG (V(D)J) genes. During affinity maturation, GC B cells undergo multiple rounds of proliferation, activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM), and selection to improve their BCR affinity for the antigen. Higher affinity cells have increased probability to be positively selected for further rounds of proliferation and SHM to further diversify, or to differentiate to memory and plasma cells, hallmarks of the adaptive immunity. B cells with increased antigen-affinity are selected due to their improved capability to capture antigen from the surface of follicular dendritic cells (FDC) and to present it to a limiting number of T follicular helper cells (Tfh). Within the GC, B cells also undergo IG class switch recombination (CSR) that leads to an exchange of the constant region of the BCR (different isotype), which influences the effector function of the B cells.

Perturbations of the germinal centre reaction (GCR) contribute to the emergence of clones expressing autoreactive antibodies or showing a transformed/malignant behaviour. Elucidating the cellular and molecular mechanisms of the GCR is essential to understand the ontogeny and evolution of BCL and RA.

 

Shared disease characteristics

Several important disease characteristics are shared between BCL and RA, such as the involvement of a disturbed GCR. In some cases similar/identical BCR specificities of the malignant B cells in BCL and autoreactive B cells in RA are found, indicating that BCL and RA can originate from similar antigenic stimuli. Chronic B-cell activation by (auto)antigen, in combination with local inflammation and decreased immune surveillance/immune checkpoints is central in the development of BCL and RA, while RA-associated lymphoproliferation represents a risk factor for developing BCL.

 

 Experimental and computational approaches

Despite recent progress, a precise understanding of the dynamics of the GCR and its role in BCL and RA pathogenesis has yet to emerge. The complexity of the GCR prompts for the development, application and integration of experimental approaches that go beyond state-of-the-art such as:

  1. Single cell transcriptomics of GC B cells;
  2. Quantitative analysis of the dynamic transcriptome and its regulation by signalling pathways;
  3. Next Generation Sequencing (NGS) analysis of the BCR repertoire to assess the clonal composition and its dynamics during the GCR;
  4. In-depth analysis of the (3-dimensional) BCR protein structures;

In addition, we need beyond state-of-the-art computational models that address specific questions related to GCR disturbances in BCL and RA, and multiscale models that integrate models at the cellular level with models at the molecular level to study how disturbed molecular pathways impact on the spatiotemporal dynamics of the GC cells.

COSMIC uses, develops, and synergistically integrates experimental and computational approaches to leverage our understanding of the role of the germinal center reaction in B-cell lymphoma and rheumatoid arthritis.

COSMIC NEWS

29 April 2018 3358

EASyM conference

2nd Conference of the European Association of Systems Medicine (EASYM) This conference is…
27 January 2018 2968

Andien Vaes: new controller

New controller: Andien Vaes. Andien Vaes (AMR) takes over the tasks of Don van Velzen.…
23 December 2017 852

Biotecture becomes Science Matters

Biotecture becomes Science Matters Our Partner Organisation Biotecture changed their name…

COSMIC Highlights

29 September 2019 74

LINK - Extremadura en el Mundo

LINK - Extremadura en el Mundo Our fellow, Rodrigo Garcia Valiente took part as an…
22 February 2019 301

CERTH Highschool students

Highschool students at CERTH Rerun by popular demand. Bastien of PLANT.ID did so well…
11 February 2018 1865

COSMIC Coffee Mug

First COSMIC Merchandise During the kickoff meeting (8-9 February) all participants…

Events

06 May 2018 763

5th European Congress of Immunology

5th European Congress of Immunology 2-5 september 2018 | Amsterdam RAI Exhibition and…
29 April 2018 1267

EASyM 2nd conference

2nd Conference of the European Association of Systems Medicine (EASYM) 7 - 9 November…
16 March 2018 2510

Workshop Applying bioinformatics and data science competency frameworks to ELIXIR Training

Workshop Applying bioinformatics and data science competency frameworks to ELIXIR…

 

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    Project coordination

    Prof. dr. A.H.C. van Kampen (Antoine)
    Bioinformatics Laboratory
    E: a.h.vankampen at amc.uva.nl
    P: +31 20 5667096

    Project management:
    Dr. Laurian Jongejan
    Department of Experimental Immunology
    E: l.zuidmeer at amc.uva.nl
    P: +31 20 5666819

    The Netherlands
    Academic Medical Center, University of Amsterdam

    Marie Skłodowska-Curie Actions

    The Marie Skłodowska-Curie actions (MSCA), named after the double Nobel Prize winning Polish-French scientist famed for her work on radioactivity, support researchers at all stages of their careers. One type of action is the European Training Network (ETN) aimed at joint research training by partners from academia, industry, and other organisation. ETNs facilitate the the researcher to experience different sectors and develop their transferable skills by working on joint research projects.

    H2020

    COSMIC is a European Training Network funded from the European Union's Horizon 2020 research and innovation programme under grant agreement No 765158.









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