Research objectives and content
hbrm is the human homologue of the yeast snf 2/swi2 gene and Drosophila brahma It encodes a nuclear protein which functions as a transcriptional activator when tethered to DNA. Furthermore, hBRM protein induces growth arrest when introduced into hBRM-deficient cells and stimulates glucocorticoid-mediated transcriptional activation through a mechanism which may involve the retinoblastoma protein (RB). Since hBRM is devoid of any putative DNA binding domain, it is probably targeted to specific genes through interactions with celluLar proteins. We propose to investigate the RB-hBRM-E2F and RB-hBRM-GR interactions and their role in growth inhibition and stimulation of transcriptional activation respectively. In addition, we will look for still unidentified proteins which interact with hBRM, allow its targeting to specific sequences and possibly mediate its activity in additional cellular processes including DNA repair.
Training content (objective, benefit and expected impact)
This research will enable me to investigate some of the most basic questions in molecular biology: regulation of cell cycle, transcriptional activation and DNA repair. The laboratory of Prof. Moshe Yaniv is one of the leading laboratories in these fields. A post-doctorate position in his group will provide me with new technical skills needed for the molecular investigation of these processes and will undoubtedly deepen and enlarge my knowledge in these domains.