PROFILE

Profile of Randy Schekman: Reflections on his first year as PNAS Editor-in-Chief hile the pace, tools, and hours in my room following all the culture of science have swimming protozoa.’’ Schekman’s ex- evolved over Randy citement with his first scientific instru- Schekman’s distinguished ment was tempered when his father Wcareer, he has continued to hold on to pointed out that it was just a ‘‘toy’’ mi- some core principles of research. In- croscope. ‘‘I remember being very up- spired in part by his mentor, Nobel set that he was being so disparaging, so laureate Arthur Kornberg, Schekman at that point I decided to buy a profes- takes a ‘‘reductionist’’ slant to sci- sional microscope.’’ He began mowing ence—identifying, separating, and puri- lawns and babysitting to save up fying the individual components of a money, but his savings never accumu- system so that each can be intently lated because his parents kept borrow- studied until its nuances are under- ing from him. stood. Schekman also believes that al- ‘‘One day, I just had enough,’’ he though new technologies certainly have says. ‘‘I rode my bike to the police sta- their place, classical techniques, such tion and told the police that I was run- as biochemical assays, remain powerful ning away from home because my approaches to tackling fundamental parents were keeping me from getting questions. As editor-in-chief, Schekman a good microscope.’’ Schekman’s father holds these same values in his vision had a stern look on his face when he for PNAS. arrived at the station to pick up his Although he expresses a desire to runaway son, but that was the after- continue to expand and modernize the noon Schekman got his Bausch and journal by bolstering online content Lomb microscope, which enabled him Randy Schekman and fine-tuning the rules governing to study his swimming microorganisms member submissions, his main goal is in a more professional manner. to turn back the clock. ‘‘This journal Cell Biology, the Annual Review of Cell An Assorted Training was considered one of the best back in Biology, and Molecular Biology of the Schekman entered the University of the 1960s and 70s,’’ he says. ‘‘When I Cell, in addition to stints on the edito- California, Los Angeles (UCLA; Los was in Kornberg’s lab, we were all rial board of several other journals. Angeles, CA) in 1966, initially choos- dying to have our papers in the Pro- And although his PNAS editorship is ing pre-med as his major because that ceedings; anything less was almost an another similarity to Cozzarelli, Schek- seemed like a natural outlet for his embarrassment. Today, things have man is clearly his own man. ‘‘Nick set interests in biology. ‘‘Then I realized changed, and other journals have risen the bar very high, and I at least want there was a whole other world at the to prominence, and we need to make to match it, but I’m not his clone; I’m university that I hadn’t really known scientists ‘want’ to put their best stuff going to try things my way.’’ in our journal again.’’ As proof, Schek- about.’’ After doing well in freshman man recalls that his first PNAS paper Swimming in Science chemistry during his first semester, Schekman was placed in an honors sec- from Kornberg’s lab was just the type ‘‘I remember the exact moment,’’ says tion taught by Willard Libby, the in- of major discovery that people wanted Schekman. ‘‘Seventh grade. I walked ventor of carbon-14 dating. One of the to publish in PNAS (1). into the school science fair, and the course requirements was to work in a Schekman took the reins of PNAS in whole world was revealed to me.’’ All chemistry laboratory, and Schekman November 2006, following in the foot- around him fellow students, some only ended up in the laboratory of Michael steps of Nicholas R. Cozzarelli just as a year older, were putting their exhibits Conrad, a molecular biologist in the he had many times before. Schekman on display, and Schekman felt the tin- chemistry department. acknowledges that his own path closely gle of competition. ‘‘Athletics weren’t ‘‘The first thing he had me do was mirrored Cozzarelli’s: studying under for me,’’ he notes, ‘‘but this was an im- read the then-first edition of a book by Arthur Kornberg; becoming a profes- mediate turn-on.’’ The following year James Watson called Molecular Biology sor of molecular and cell biology at the he began exhibiting his own science of the Gene, which really opened my University of California, Berkeley projects, a pursuit that he would con- eyes. I remember reading it in my lei- (Berkeley, CA); and assuming the chair tinue over the course of his high sure time like it was the Bible.’’ The of the National Academy’s biochemis- school years, winning awards and acco- combination of that book and his labo- try section. Just as Cozzarelli was able lades along the way. On three occa- ratory experience quickly scuttled to talk to a variety of scientists, Schek- sions, the precocious Schekman Schekman’s medical aspirations and sent man’s academic background—from his advanced from his local high school him on the path toward academic early training focused on biochemistry competition in Anaheim to the Califor- science. and his longstanding work on the me- nia State Science Fair. ‘‘Every year was At UCLA, Schekman quickly found chanics of the secretory pathway—has a new adventure,’’ he says of the time. himself in the minority among his fel- enabled him to intelligently cross a His adventures began with pond low biology majors, who were taking multitude of scientific disciplines. scum, of all things. ‘‘I was fascinated only the courses for their pre-med re- Schekman also brings two decades of with all the tiny things that lived in the editorial experience to PNAS, includ- water,’’ he says, ‘‘so I got a little toy ing turns as editor of the Journal of projecting microscope, and I spent © 2008 by The National Academy of Sciences of the USA

www.pnas.org͞cgi͞doi͞10.1073͞pnas.0610781105 PNAS ͉ February 26, 2008 ͉ vol. 105 ͉ no. 8 ͉ 2763–2765 Downloaded by guest on September 29, 2021 quirements and were not especially in- portant to head off and do something ‘‘Even though I consciously chose terested in science. During his sopho- new.’’ yeast as my model because it was ma- more year, he thought about That attitude proved fortunate, be- nipulable, I didn’t think I would ever transferring to another school, until he cause Schekman ended up working on use much genetics,’’ he says. ‘‘But after discovered a program for education a relatively obscure phenomenon: the my first attempts failed, I thought, ‘All abroad. One of Schekman’s professors difference in endocytosis that was ob- right, I guess we’ll just have to isolate mentioned a potential destination, not- served between neonatal and adult red mutants.’’’ With the aid of a pair of ing that the eminent bacterial geneti- blood cells (2). ‘‘Having worked with highly skilled laboratory members, cist William Hayes had just started a graduate student Peter Novick and Medical Research Council (MRC) unit technician Charles Field, Schekman at the University of Edinburgh (Edin- ‘‘When I was in soon had dozens of mutants ready. Of burgh, U.K.). Schekman was accepted course, he didn’t know whether any of to spend his junior year there. Kornberg’s lab, we were them would pan out, but one day Nov- ‘‘After I was accepted to this pro- ick called him over to look in the gram,’’ recalls Schekman, ‘‘I wrote to all dying to have our microscope. ‘‘The moment I saw that Hayes to express my interest in work- mutant was accumulating vesicles, I ing for him. However, he mistakenly papers in the knew that we were going to have 20 or thought I was a sabbatical visitor, so 25 years of work based on continuing when I arrived they already had set me Proceedings; anything that path.’’ Schekman had just found up with my own office, complete with his first secretion mutant, sec1 (3). my name on the wall, and even had me less was almost an Over the next few years, Schekman listed in their program as a visiting sci- and Novick would characterize numer- entist from UCLA.’’ The confusion was embarrassment. We ous other sec mutants, which affect all quickly cleared up, and Schekman pro- exits of the membrane traffic highway, ceeded to have a wonderful time, even need to make scientists from the endoplasmic reticulum (ER) though he didn’t get to keep his office. to the cell surface (4). If there were After returning to UCLA for his se- ‘want’ to put their best any drawbacks to their plethora of nior year, Schekman continued to be findings, it was that people started consumed by laboratory work, to the stuff in our journal thinking of Schekman as a geneticist. point that he eventually stopped going ‘‘When this work was first getting pub- to classes and his grades began to suf- again.’’ lished, I kept getting all these inquiries fer. ‘‘I had become so determined to from postdocs and students who work in a lab that I found course work wanted to do yeast genetics. And I to be too artificial,’’ he says, adding microorganisms in the past, I felt that kept trying to convince them to use that his academics didn’t drop too when I was ready to start my own ca- the mutants to establish biochemical badly, noting that he still managed to reer, I would return to microorgan- assays.’’ Schekman hoped all along to get accepted to Stanford University isms.’’ He eventually settled on yeast, use the mutants to study the mecha- (Stanford, CA) for graduate school, which was easy to grow and genetically nisms of transport in yeast, in a way which had one of the premiere bio- manipulable. Beyond that, research in similar to Stanford’s Jim Rothman chemistry departments at the time. yeast membrane assembly lagged be- (who would later share the 2002 Schekman had developed an interest hind that of animal cells and seemed Lasker Award for Basic Medical Re- in DNA replication while working in the to be an area ‘‘ripe for investigation.’’ search with Schekman), who had devel- laboratory of Dan Ray at UCLA and Soon after, in 1976, Schekman was ap- oped an in vitro system of measuring had chosen Stanford specifically for the pointed as an assistant professor at Golgi transport by using mammalian chance to work in that field under Berkeley. cell lysates. Arthur Kornberg. ‘‘Maybe I was a little For a while, Schekman’s group strug- too narrow-minded,’’ Schekman says, Entering a Budding Discipline gled with trying to mimic this system in ‘‘but I knew exactly that I wanted to Schekman’s eagerness and admitted yeast cells, which have less membrane learn how to dissect a problem biochem- naivety about yeast—his only experi- transport activity than animal cells. Then, ically, and I knew [Kornberg] was going in 1985, David Baker, another gifted grad- ence was a crash course on yeast ge- to teach me what I wanted to learn.’’ uate student—‘‘a true dynamo,’’ says netics he took at Cold Spring Harbor At Stanford, Schekman befriended Schekman—joined the laboratory and Laboratory (Cold Spring Harbor, NY) postdoc Bill Wickner, who proved to began developing a functional cell-free be a bit of a muse on two different after completing his postdoc— system. ‘‘He essentially managed to repro- fronts. First, he introduced Schekman contributed to a somewhat rocky start duce the first half of the secretory to the woman who later became his to his career as a principal investigator. pathway in vitro, and these reactions reca- wife, Nancy; second, he helped per- His first grant attempt was rejected for pitulated the normal process, because suade Schekman to consider studying a lack of necessary details, and his first mutant lysates were defective compared to biological membranes. experiments likewise met with failure. non-mutant cell lysates’’ (5). At that time, Jonathan Singer at the ‘‘I was thinking too much like a bio- The first protein to be uncovered by University of California at San Diego chemist,’’ he says. ‘‘I initially thought this system was the product of the sec23 (La Jolla, CA) had just published his that we could grow up large quantities gene, which is critical for transport be- fluid mosaic model of membrane struc- of yeast and then inhibit secretion by tween the ER and the Golgi apparatus ture. ‘‘Since he clearly was doing the some chemical means, allowing us to (5). sec23 didn’t act alone in this process, most creative work on the subject, I accumulate intermediates in the pro- and soon Schekman found that six pro- went to postdoc with him, not neces- cess. That didn’t work.’’ Fortunately, teins (Sec23, Sec24, Sec12, Sec13, Sec31, sarily to pick up a project, but so I that short-term failure would lead to and Sar1) were required to bud vesicles could learn the field. I felt it was im- long-term success. from the ER; Schekman named this com-

2764 ͉ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0610781105 Zagorski Downloaded by guest on September 29, 2021 plex COP-II (to distinguish it from an- nary nature of current scientific research version of the formerly staid journal Cell other protein assembly necessary for intra- calls for the journal to keep pace. In Regulation. He acknowledges the daunt- Golgi transport named COP-I). This particular, he notes that the word count ing challenge of achieving his lofty aspi- complex has been a major focus of his limits imposed by many journals, includ- rations among all the competition in research in the dozen years since its ing PNAS, may cause researchers to modern publishing but believes that, in discovery (7). gloss over some of their data or even time, this classic can be restored. ‘‘When I was in college and getting into science, Further probing revealed that COP-II discourage them from submitting their I’ll never forget those first moments sur- not only pinches the buds from the work. Last year the journal launched a veying dusty old journals in the library, membrane but also recruits the correct Feature Article category to encourage and there was the Proceedings. I vividly protein cargo. Schekman’s findings submissions of exceptional breadth and remember looking through it, and just helped establish that the secretion path- importance (8). Other ideas Schekman the feel of it was alluring to me. And way mediates the highly complex sorting has for improving the journal can be for people in college today who are and transport of proteins. found in his recent editorial, ‘‘Charting making their career choices, I would like the course for PNAS’’ (9). to project—obviously not in the stacks Bringing Back the Golden Age This is not Schekman’s first time of the library, but on the screen of a When he thinks about his tenure as sprucing up a journal. In 1992 he be- home PC—that same allure of science. PNAS editor-in-chief, Schekman says came one of the founding editors of Mo- That’s what the Proceedings can do.’’ that the fast progress and interdiscipli- lecular Biology of the Cell, a revamped Nick Zagorski, Science Writer

1. Brutlag D, Schekman R, Kornberg A (1971) A of Saccharomyces cerevisiae. Proc Natl Acad Sci USA endo-plasmic reticulum to the Golgi complex in vivo possible role for RNA polymerase in the initiation 76:1858–1862. and in vitro. EMBO J 8:1677–1684. of M13 DNA synthesis. Proc Natl Acad Sci USA 4. Novick P, Field C, Schekman R (1980) Identification of 23 7. Barlowe C, et al. (1994) COPII: A membrane 68:2826–2829. complementation groups required for post-translational coat formed by Sec proteins that drive vesicle 2. Schekman R, Singer SJ (1976) Clustering and endocyto- events in the yeast secretory pathway.Cell 21:205–215. budding from the endoplasmic reticulum. Cell sis of membrane receptors can be induced in mature 5. Baker D, Schekman R (1989) Reconstitution of protein 77:895–907. erythrocytes of neonatal but not adult humans. Proc transport using broken yeast spheroplasts. Methods 8. Schekman R (2007) Introducing feature articles in Natl Acad Sci USA 73:4075–4079. Cell Biol 31:127–141. PNAS. Proc Natl Acad Sci USA 104:6495. 3. Novick P, Schekman R (1979) Secretion and cell-surface 6. Hicke L, Schekman R (1989) Yeast Sec23p acts in the 9. Schekman R (2008) Charting the course for PNAS. Proc growth are blocked in a temperature-sensitive mutant cytoplasm to promote protein transport from the Natl Acad Sci USA 105:2754–2755.

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