WP1 Alpha-synuclein structure: Detection and biomarkers (MPI, Farfield, UniLanc)

Collaborative studies:

Zweckstetter and Kirik: Development of F18- or C11-labeled molecules for in vivo ASYN oligomer imaging; Zweckstetter and Jensen: Influence of ASYN-interacting molecules on oligomerization; Zweckstetter and Farfield/Allsop: Influence of membrane interactions on ASYN oligomerization; Zweckstetter and Outeiro: Influence of ASYN phosphorylation on ASYN oligomerization; Farfield and Allsop: DPI for detection of ASYN conformations; Farfiled-Allsop and Kahle-Stefanis-Jensen-Reiss-Kahle-Outeiro-Kirik: Detection of ASYN conformations in cell or animal material

WP2 Pathogenic effects of alpha synuclein: models and pathways

(BRFAA, Uni Aarhus, Uni Tuebingen – Kahle, Uni Lund, Uni Tuebingen – Riess/Nuber)

Collaborative studies:

Stefanis and Kirik: Virally-mediated overexpression of modifiers of ASYN degradation in vivo; Stefanis and Boehringer-Ingelheim: ASYN degradation; Jensen and Stefanis-Kahle/Reiss: ASYN oligomer-binding proteins in neuronal cell and mouse models; Kirik and Zweckstetter: Towards development of novel PET-based imaging of ASYN oligomers in vivo; Kirik and Riess: Standardization of behavioural testing; Riess and Stefanis: ER stress/Cell Death/Autophagy in a “humanized” PD mouse model; Riess and Boehringer-Ingelheim: Generation of “humanized” PD mouse model, Kahle and Outeiro/Bioalvo: Validation of ASYN modifiers in vivo; examination of concurrent tauopathy.

WP3 Experimental therapeutics targeting alpha-synuclein: screening and validation

(Boehringer-Ingelheim, IMM Lisbon, Bioalvo)

Collaborative studies: 

Bioalvo and Outeiro-Stefanis: Validation of candidate genes in ASYN/Tau transient or inducible co-expression mammalian cell models Outeiro and Bioalvo: Small molecule screens in yeast models of synucleinopathies. Outeiro and Stefanis: Effect of post-translational modifications on ASYN degradation Outeiro and Kirik: Effect of post-translational modifications on ASYN toxicity in vivo Boehringer Ingelheim and Riess: Generation and characterisation of humanized DDQ ASYN mice. Boehringer Ingelheim and Kahle: Characterisation of transgenic mouse models. Boehringer Ingelheim and Stefanis-Outeiro: Development of cellular assays.