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NLR-proteins in Immunity and Inflammation

NLR-proteins in Immunity and Inflammation

Objective

A growing number of acute and chronic inflammatory disorders including Crohn's and Inflammatory Bowels's disease have recently been linked to mutations in a new family of immune receptors, termed NLRs (Nucleotide Oligomerization Domain and Leucine Rich Rep eat containing Receptors) (Martinon, Trends Immunol 2005). NLRs recognize pathogens inside the cell and initiate, much like Toll like receptors, a series of signalling processes that stimulate and orchestrate the innate and adaptive immune responses.

Despite their importance, the ligands, specificity and mechanisms of most NLRs are unknown. In order to identify their physiology and respective roles in human infections and inflammatory diseases, we will characterize the function of NLRs by biochemical and structural means. Functional analysis is the key to understanding the molecular mechanisms of disease and represents the new front-line and limiting factor for realizing potential benefits of genome-based science and stem cell research. Using an integrative and parallelized approach, Robert Schwarzenbacher and his colleagues contributed functional studies in the fields of immunity (EMBO J 1999), apoptosis (Cell 2000), enzymology (PNAS 2004), as well as drug discovery (Nat. Struct. Mol. Biol. 2004).

Moreover, they recently unravelled the structure and function of the apoptotic protease activating factor 1 (Apaf-1) (Nature 2005), the first prototype of huge signalling platforms and a close relative of NLRs. Prof. Schwarzenbacher will bring his unique expertise in functional characterization and high throughput methodology gained at the Joint Centre for Structural Genomics back to Salzburg to create a new European centre of excellence. A primary goal of his team is to generate a platform for the development and application of functional studies in order to understand signal proteins and their complexes involved in disease and to use this information for the development of novel therapies.

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Coordinator

PARIS LODRON UNIVERSITÄT SALZBURG

Address

Kapitelgasse 4-6
Salzburg

Austria

Administrative Contact

Anna Maria FRISCHAUF (Prof.)

Project information

Grant agreement ID: 33534

  • Start date

    1 October 2006

  • End date

    30 September 2010

Funded under:

FP6-MOBILITY

Coordinated by:

PARIS LODRON UNIVERSITÄT SALZBURG

Austria