RNA Polymerases (Pol I, II and III) constitute the centerpiece of the intricate molecular machinery that transcribes the genetic code into RNA and controls such diverse processes as cell differentiation, development, and responses to environmental change. Specifically, Pol II transcribes protein-coding genes into messenger RNA (mRNA). In turn, mRNA serves as a template for the synthesis of proteins by the ribosome. Therefore, Pol II functions as the critical intermediary in transforming the genetic code into the myriad of proteins that are the building blocks of all living organisms.
Gene transcription is a complex and highly regulated process. While structural knowledge is beginning to emerge, little is understood about the molecular-level mechanisms that underlie gene expression. At the same time, detailed mechanistic knowledge is essential to advance biomedical applications.
The principal aim of Ivanov’s project is to unravel the molecular architecture and functional dynamics of transcription pre-initiation (PIC) complexes, which are critical for gene regulation. The team will take advantage of new cryo–electron microscopy data and combine it with advanced computational modeling on the Summit machine at OLCF to elucidate the mechanisms of PIC assembly, promoter recognition, DNA melting, and the roles of general transcription factors therein.
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