From Rat Tails to Glycoproteostasis: Motivated by Biology, Enabled by Biophysics, and Lucky

Abstract

In this article I tell the story of my career path and how I have come to focus my research on protein folding in the cell. My early fascination with protein folding began during my undergraduate research. My graduate work exploited reductionist approaches to explore structural features in proteins by using cyclic peptide models ofβ-turns. My career trajectory from these early days to present, described in the first section of this article, illustrates the importance of pursuing the scientific questions that one finds most exciting and seizing professional opportunities that enable these questions to be tackled productively. In addition, this trajectory shows how serendipity can shape a career path. The second section describes the extraordinary scientific discoveries I have witnessed in protein folding during my career. Here I explain how I was drawn into the world of protein folding in thecell. This turning point allowed me to participate in the explosion of research on molecular chaperones in the early 90's and to help elucidate the nature of chaperone-substrate recognition, a problem I continue to focus on. Examples of our research contributions are presented in the third section, with a perspective on major challenges for the future offered in the last section. Throughout my career I have engaged in many collaborations;each has opened new scientific doors. Importantly, I seek to instill in my trainees the same excitement about research that I feel and to foster their growth as scientists and their discovery of their own passions and talents.

Keywords: chaperones; cyclic peptides; protein folding; protein homeostasis; signal sequences/protein secretion.