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Protein aggregation diseases (b/d PAD)

Protein aggregation diseases (PAD), exemplified by Parkinson’s or Alzheimer’s disease and systemic amyloidoses, are characterized by an abnormal deposition of protein aggregates of regular three-dimensional structure (amyloid). The B/D PAD working group aims at developing proteomics assays for proteins that are relevant to the study, diagnosis and therapy of protein aggregation diseases. These assays are tested and refined on a set of relevant patient samples (for clinical applications) and on samples from model organisms and cell culture (for basic research). The assays are made publicly available through web-based databases such as PRIDE. The assays consist of validated coordinates for targeted proteomic assays and spectral libraries from shotgun proteomics measurements. We also generating SWATH/data-independent fragment ion maps for relevant samples. Besides developing assays for measuring protein abundances, a peculiarity of our initiative is that it attempts also the development of proteomics assays for “aberrant protein conformations”, those typically generated in PADs. The idea relies on a recently developed structural proteomic approach based on limited proteolysis and mass spectrometry (LiP-MS). Mass spectrometric assays for “functional” and “pathological” conformational states of amyloidogenic proteins will also be applied to clinical and biological samples and be made publicly available through publicly accessible databases.

Clinicians actively involved in the PAD working group support the transfer to clinical practice of the developed methods, such as assays to quantify specific disease-related proteins and their fragments in biofluids and multiplexed MS-based methods for the diagnosis and typing of systemic amyloidosis. We believe that the increasing availability of tools to precisely measure proteins involved in PADs will positively impact research on the molecular bases of these diseases and support early disease diagnosis and a more-confident subtyping.

    Current lines of work:

    • Definition of priority protein lists relevant in PADs
    • Development of standardized targeted and unbiased methods for the detection and quantification of clinically relevant proteins
    • Evaluating the potential use of such assays for the diagnosis and subtyping of local and systemic amyloidoses and the possibility of transfering them to the clinical environment
    • Identification of novel proteins relevant to protein aggregation diseases by unbiased proteomic screens
    • Structural analysis of proteins involved in PADs using structural proteomics tools (such as LiP-MS); development of mass spectrometric assays to monitor healthy and pathological conformational states of proteins involved in PADs and evaluation of the concept of “conformational biomarkers of disease”.

      Current group members:

      1. Paola Picotti (ETH Zurich, CH, chair) (Proteomics, MS)
      2. Michelle Hill (Univ. of Queensland, Australia, co-chair) (Proteomics, MS)
      3. Bouke Hazenberg (Univ. of Groningen, NL) (Clinician)
      4. Gyorgy Marko-Varga/Melinda Rezeli (Univ. of Lund, Sweden) (Proteomics, MS)
      5. Roman Zubarev (Karolinska Inst., Sweden) (Proteomics, MS)
      6. Giampaolo Merlini (University of Pavia, Italy) (Clinician)
      7. Catherine Costello (Boston Univ., MA, USA) (Proteomics, MS)
      8. Erik Portelius (Univ. of Gothenburg, Sweden) (Proteomics, MS)
      9. Kaj Blennow, (Univ. of Gothenburg, Sweden) (Clinician, Proteomics, MS)
      10. Junichi Kamiie (Azabu Univ., Kanagawa, Japan) (Proteomics, MS)
      11. Magdalini Polymenidou (Univ of Zurich, CH) (Biologist)
      12. [Susan Lindquist, WIBR, Cambridge, MA, USA (2014-2017)] (BIologist)

      Links:

      Papers:

                Leadership:

                Paola Picotti, Chair

                Michelle Hill, Co-Chair

                For more information or participation opportunities please contact office(at)hupo.org.



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