Molecular and cellular biology of the extended DISC1 pathway.
DISC1 can be found as an insoluble aggregate in post mortem brains of a subpopulation of patients with CMI (20%), and subsequent research established that DISC1 aggregation propensity was dependent on disease-associated polymorphisms, and led to both loss and gain-of-function effects.
Major SCZ candidate genes are converge at the protein level to the extended DISC1 pathway. In this work package, DISC1 multimerization is investigated with biophysical, biochemical and microscopic techniques, including for posttranslational modifications of full length non-mutant DISC1.
The key objectives are
- to characterize the structure of DISC1 and its disease-relevant ligands in vitro and in vivo
- to investigate its cellular pathology
- to explore the molecular biology of VGF, a novel member of the extended DISC1 pathway.