Biophysics Seminar<br>Principles of Co-Translational Folding: From Pathways to Proteome<br><b>Speaker: Edward O'Brien (University of Cambridge)</br></b>

Speaker: Edward O'Brien (University of Cambridge)

Understanding and manipulating protein folding and protein homeostasis in living cells is one of the great challenges facing this generation of biophysicists. It requires that we understand the concomitant folding of proteins during their biosynthesis by the ribosome molecular machine, a factor shown to be important in determining the cellular concentration of successfully folded proteins. I will discuss my efforts to understand the physical principles of such co-translational folding through the development of coarse-grained simulation force-fields, chemical kinetic modeling, and systems biology methods. I will show how these tools have allowed us to gain novel insights into fundamental issues of in vivo folding, including the impact of variable translation rates and synonymous codon usage, the effect of chaperones, and, at the cellular level, the co-translational folding properties of the E. coli proteome under different growth conditions. These methods are opening up new avenues of research in the areas of synthetic biology, biotechnology and biomedicine, where, for example, they provide a framework for rationally redesigning transcriptomes to yield cells with desirable proteostasis properties.