Project Summary

Naoya Sawamura, Ph.D. (Young Investigator 2005) of Johns Hopkins School of Medicine, plans to study the molecular biology of the product of the Disrupted-in-Schizophrenia-1 (DISCI) gene , which is located at the breakpoint of a chromosomal translocation co-segregating with major mental illness in a large Scottish family. Although the function of DISCI is still unclear, nuclear localization signals and leucine-zipper motifs in DISCI suggests its role in the nucleus. In this study, Dr. Sawamura will explore the function of nuclear DISCI using molecular and cell biological methods. First, Dr. Sawamura will determine the domains that regulate its nuclear function and will focus on its nuclear localization signal, nuclear export signal and leucine-zipper motif. Dr. Sawamura also will explore functions of nuclear DISCI, such as transcriptional activity and DNA binding. Additionally, Dr. Sawamura will examine the nuclear predisposition of DISCI in autopsied brains from control subjects as well as patients (schizophrenia, bipolar disorder, major depression). Preliminary data from Dr. Sawamura suggests that DISCI levels are greater in the nucleus of the brains from patients with schizophrenia and major depression. Further, the laboratory will focus on a genetic variation in a leucine- zipper motif and examine if this change influences the nuclear localization of DISCI. Information about nuclear DISCI could help clarify the pathophysiology of schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

Search Again