Ramanujan Hegde: The prion puzzle and protein translocation

P rotein translocation from the cyto-sol into the endoplasmic reticulum (ER) is generally considered a reasonably well understood, automatic process. But getting proteins into the ER is actually a highly regulated process that poses more of a conundrum for the cell than it seems, especially under challenging metabolic conditions like ER stress (1). What's more, aberrant or incomplete protein translocation can give rise to disease— which Ramanujan Hegde has shown can happen with prion protein (PrP) (2, 3). Throughout his career, Hegde has worked through the puzzle of protein translocation. His laboratory at the National Institutes of Health focuses on trying to understand how cells regulate protein translocation (4, 5) and how certain proteins like PrP can illuminate these enigmas, bringing new insights to normal processes (1) and to the development of prion disease (3). In a recent interview, we asked Hegde how he thinks through these problems and how he's approached a career in research. Did you have any role models growing up? My parents were both strong role models for me. My father's family comes from a small village in rural India, and they are all farmers. But my father injured his foot when he was very young and couldn't work in the fi elds, so his only option was to study— that's how he got interested in mathematics. He was self-taught at fi rst, but eventually he went to a local college , and then my family emigrated to Saskatoon, Canada when I was about six years old so that he could pursue a PhD there. A couple of years later, we moved to DeKalb, Illinois. It took a lot of internal drive to get him where he is today, which is one of the things I've always really admired about him. My mother, too, has that kind of drive, although she put aside a lot of her interests and education until her kids were grown up. She was a homemaker until my brother and I were about high school age, then she got a Bachelor's degree at the college in DeKalb and pursued a career in computer science. I think the fact that both my parents hold education so central to their lives, and also that it was central to our immigration to the West, was very inspirational for me. I feel that I have a special set of opportunities that I might not otherwise have …