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.

 

Work package 3.  B-cell lymphoma (BCL)

Work package leader: Dr. Jeroen Guikema.

 

Research question: What is the precise role of the germinal center (GC) reaction in B-cell tumorigenesis?


Several of the most frequent B-cell cancer subtypes are considered of GC B-cell origin, indicating that GCR shutdown failure lies at the core of their genesis and evolution. B-cell lymphoma (BCL) of postulated GC origin, including diffuse large B-cell lymphoma, follicular lymphoma and a subset of chronic lymphocytic leukemia, exhibit somatic hypermutation (SHM) patterns typical of B cells that have undergone selection by antigen. This is often accompanied by intraclonal diversification due to SHM arising in a context of ongoing antigen interactions, while at least some BCL display in vivo class switch recombination (CSR). Alltogether attesting to the importance of the GCR in their genesis and progression. Moreover, these neoplasias are characterised by recurrent gene mutations/translocations that, at least in part, stem from aberrant and/or off-target SHM and/or CSR . In particular, error-prone DNA repair activities that are characteristic for GC B cells by enabling B-cell receptor (BCR) diversification, facilitate the acquisition of secondary genetic alterations ultimately causing malignant transformation. Most experimental (mouse) models for BCL focus on the endpoints of malignant B-cell transformation, whereas the early stages of GC-derived B-cell tumorigenesis are poorly understood, and efforts to reconstruct the multistep process of tumorigenesis have been rather limited. Moreover, the GC B-cell specific regulation of DNA repair fidelity, and the effects of GC B-cell specific oncogene overexpression on GCR resolution (embodying the early stages of tumorigenesis) remain largely uncharted.

COSMIC aims to provide a high-resolution framework of molecular, cellular and clonal dynamics of the normal and BCL GCR, assess the GC-specific regulation of DNA repair activities, and to assess the effects of overexpression of BCL-associated oncogenes in the GC. We expect that this will lead to biomarkers that predict onset of BCL, and to molecular pathways essential for BCL growth and maintenance that can be targeted with (new) drugs. The expression and/or activity of the identified biomarkers will be validated and tested in human BCL patient samples and normal human lymphoid tissues containing GCs (reactive lymph node and tonsil).

Expected results: Novel mechanistic insight into the role of the GCR in B-cell tumorigenesis, identification of crucial factors/steps that determine transformation, growth, and maintenance of malignant GC B cells. Novel therapeutic biomarkers and drug targets.

 

Go to Work package overview 

COSMIC NEWS

29 April 2018 2647

EASyM conference

2nd Conference of the European Association of Systems Medicine (EASYM) This conference is…
27 January 2018 2096

Andien Vaes: new controller

New controller: Andien Vaes. Andien Vaes (AMR) takes over the tasks of Don van Velzen.…
23 December 2017 657

Biotecture becomes Science Matters

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

COSMIC Highlights

22 February 2019 137

CERTH Highschool students

Highschool students at CERTH Rerun by popular demand. Bastien of PLANT.ID did so well…
11 February 2018 1471

COSMIC Coffee Mug

First COSMIC Merchandise During the kickoff meeting (8-9 February) all participants…
11 February 2018 794

Kickoff meeting

COSMIC kickoff meeting. 8-9 February, 2018 Amsterdam COSMIC officially started 1st of…

Events

06 May 2018 557

5th European Congress of Immunology

5th European Congress of Immunology 2-5 september 2018 | Amsterdam RAI Exhibition and…
29 April 2018 991

EASyM 2nd conference

2nd Conference of the European Association of Systems Medicine (EASYM) 7 - 9 November…
16 March 2018 1421

Workshop Applying bioinformatics and data science competency frameworks to ELIXIR Training

Workshop Applying bioinformatics and data science competency frameworks to ELIXIR…

 

  • amc-small.jpg
    marie_curie_actions-small.png
    EU-flag-small.gif

    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.









© 2018 COSMIC. All Rights Reserved.

Please publish modules in offcanvas position.