"Emerging biochemical and biophysical data strongly suggest that the transformation of the potential set of proteins, encrypted in the genome, into its actual vital functional set, is a manifestation not just of the genetic code, but of an additional layer of information encoded within the newly synthesized polypeptide nascent chain. To date, we know that immediately upon the first steps of protein synthesis, a variety of signals are formed within the evolving nascent chain (NC). These signals, by acting directly on the ribosome or by recruiting additional cellular machines, have the ability to direct new steps in the transformation of the NC and guide it towards the acquisition of its final functional state and cellular location. Due to its distinct nature, I will refer this ensemble of signals as THE NASCENT CODE. Despite our knowledge of its existence, we know very little about its mechanism of action. The goal of this research is to unravel the molecular determinants of the nascent code and to decipher how the signals, embedded in the primary sequence of the NC, orchestrate the concerted action of the ribosome and its ancillary factors (i,e, SecA, TF). The approach entails the reconstructing of the process describing the birth of a protein and following its progress over time. The techniques used in the analysis of this process, namely fluorescence spectroscopy, Cryo electron microscopy, solid state NMR-DNP, solution state NMR and X-ray crystallography, will illuminate macroscopic to atomic level details of the dynamics, structure and interactions of the key players involved. The realization of this research project will allow us to understand an essential process in the cell, for which very little structural information is currently available, and provide the structural foundation to intervene and control this process for biotechnological or therapeutic reasons."
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