NLR proteins in immunity and inflammation

  • Schwarzenbacher, Robert, (Principal Investigator)
  • Ehart, Angela, (Co-Investigator)
  • Lindner, Katharina Anna Maria, (Co-Investigator)
  • Pröll, Martina, (Co-Investigator)

    Project Details

    Description

    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 Repeat containing Receptors). 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 how NLRs function 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, Prof. Robert Schwarzenbacher and his colleagues recently unraveled the structure and function of the apoptotic protease activating factor 1 (Apaf-1), the first prototype of huge signaling 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 Center for Structural Genomics, La Lolla, CA, back to Salzburg, Austria 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 NLR signal proteins and their complexes involved in disease and to use this information for the development of novel therapies

    The following qualitative indicators will be used to monitor and validate progress of the three different phases, start, ongoing and finalization in the underlying project

    project start:
    - MCEXT team
    formation of team: hire team members and establish workplaces according to implementation plan
    - scientific progress
    launch experimental work, cloning, expression and purification of NLR proteins

    ongoing project:
    - MCEXT team
    satisfaction of team, number of workshops, summer schools, and training courses organized and participated
    - scientific progress
    status of experimental work, number of NLRs cloned, purified, and characterized, number of collaborations

    project finalization:
    - MCEXT team
    satisfaction of team, number of scientific meetings participated, number of scientific exchange visits independence as researchers, interdisciplinary skills, promotion of young female academics
    - scientific progress
    number of NLRs characterized, follow-up projects submitted, number of collaborations, papers submitted and published citations

    - to elucidate the structure and function of NLRs
    - to identify the molecular details of pathogen recognition and activation of NLRs
    - to study the mechanism of NLR signalling
    - to assess the molecular pathophysiology of NLR-mutations in inflammatory disorders
    Short titleNLR's in Immunity
    StatusFinished
    Effective start/end date1/10/0630/09/10

    Fields of Science and Technology Classification 2002

    • 1411 Molecular biology