SP 8

Interactome networks and perturbed cellular functions in schizophrenia and bipolar disorder

Schizophrenia and bipolar disorder are multifactorial disorders. Besides environmental factors, their clinical manifestation may involve the contribution of hundreds to thousands of genetic risk factors. Large national and international research efforts are now identifying many of the respective risk genes. Subproject 8 (SP8) investigates interactions between the gene products (proteins) of both established risk genes and novel genes identified within IntegraMent (in cooperation with SP1, SP3, SP6 and SP7). This research approach is of key importance, since for many of these risk genes, cellular function and/or their role in the underlying disease mechanisms remains unclear.

High validity protein-protein interaction network, specific for schizophrenia. This network comprises 4302 proteins (nodes) and 7991 interactions (lines). The red protein symbols indicate an association with schizophrenia. The network is the result of the combining of our high through-put sequencing with data from HIPPIE, a public interaction-database. A comparable network is currently being created for bipolar disorder.

SP8 has developed and applied a computer-based approach to demonstrate comprehensive protein-protein interaction networks. In a second step, these networks undergo extensive experimental validation. Based on our preliminary results and by applying bioinformatic calculations, we were able to predict highly-connected protein clusters, i.e., interrelated groups of proteins. In collaboration with SP1, SP6, and SP7, we will now integrate defined datasets into the networks in order to refine the newly identified protein-protein interactions further. In addition, we will collaborate with SP2 and SP9 to investigate how specific (already known) genetic risk factors may interfere with or disturb functional protein complexes and cellular equilibrium.