CORDIS
EU research results

CORDIS

English EN

Regulation and Function of CARD9 / BCL10 / MALT1 Signalosomes in Innate Immunity and Inflammation

Project information

Grant agreement ID: 322865

Status

Closed project

  • Start date

    1 February 2013

  • End date

    31 January 2019

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 440 200

  • EU contribution

    € 2 440 200

Hosted by:

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Germany

Objective

Acute inflammation is a response to infection or tissue damage that is critical for host protection and tissue homeostasis. However, deregulated or chronic inflammation is harmful to the host and can cause multiple diseases including inflammatory bowel disease, rheumatoid arthritis, cardiovascular diseases, neuroinflammatory disease and cancer. Cells of the innate immune system sense microbial or sterile danger via pattern recognition receptors (PRRs). Subsequently, these PRRs engage intracellular signalling modules to elicit inflammatory effector mechanisms. We have recently identified the CARD9 / BCL10 / MALT1 (CBM) signalosome as a central proinflammatory signalling complex in innate immune cells. This molecular platform responds to stimuli from transmembrane SYK-coupled C-type lectin receptors and from intracellular danger sensors such as RIG-I-like helicases, NOD2 and presumably others to robustly activate NF-κB and MAPK pathways. Innate CBM signalling is engaged upon fungal, bacterial or viral recognition and upon sterile cell injury and it is essential for host protection in humans and mice. Still, it is unclear how the CARD9 / BCL10 / MALT1 signalosome is activated on a molecular level and how CBM responses are transduced to effector cascades. Moreover, although CARD9 polymorphisms are linked to various human inflammatory diseases, the cell type- and signal-specific roles of CBM signalosomes in complex diseases in vivo are unknown. Here we aim to take an integrated genetic, biochemical and in vivo approach to comprehensively dissect the regulation of the CARD9 / BCL10 / MALT1 complex in innate immunity and to define the role of this signalosome in clinically relevant inflammatory diseases. Mechanistic in vitro studies will be combined with the in vivo analysis of CBM function in genetically defined mouse models to gain better insights into the regulation of innate immunity and to pave the way to novel therapeutics for inflammatory diseases.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Principal Investigator

Jürgen Maximilian Ruland (Prof.)

Host institution

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Address

Ismaninger Strasse 22
81675 Muenchen

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 440 200

Principal Investigator

Jürgen Maximilian Ruland (Prof.)

Administrative Contact

Beate Schaulin (Ms.)

Beneficiaries (1)

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Germany

EU Contribution

€ 2 440 200

Project information

Grant agreement ID: 322865

Status

Closed project

  • Start date

    1 February 2013

  • End date

    31 January 2019

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 440 200

  • EU contribution

    € 2 440 200

Hosted by:

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN

Germany