Randy Schekman shared the 2013 Nobel Prize for Physiology and Medicine with James Rothman and Thomas Südhof for their groundbreaking work on a major cellular transport pathway called membrane vesicle trafficking. He is a Howard Hughes Medical Institute (HHMI) investigator and professor at the University of California, Berkeley. In The Nobel Journey Part I and II on Reason with Science, he talks about his early-career experiences, his laboratory’s research, his outlook on scientific publishing, and the genesis of the scientific journal eLife.
An opportune experiment with a toy microscope got Schekman interested in science as a young boy. “I had a toy microscope, and I was fascinated by these microorganisms swimming and crawling around in a drop of pond scum,” he said. “I just couldn’t believe there is another world of equivalent complexity [to ours], and somehow it captivated me, and I continued to be fascinated by microorganisms throughout my career.” Many more such stories about Schekman’s family history, childhood, and early scientific journey have been recounted in his Nobel Prize biographical piece.
Schekman had initially planned on going to medical school but working in a research laboratory as an undergraduate student changed his life. “The professor I was working with gave me a book that he said I needed to read. It was called ‘Molecular Biology of the Gene’,” Schekman said. “It was written in a style that was captivating, and I realized at that point that my life is going to be in the basic science of cellular processes and not in medicine.”
Schekman pursued his Ph.D. with the biochemist and Nobel Laureate Arthur Kornberg, and studied DNA replication at Stanford University. Kornberg was instrumental in teaching Schekman how to approach a complicated scientific problem.
As a post-doctoral researcher, Schekman changed fields and worked with biological membranes. Membranes are phospholipid layers that enclose the cell and several organelles within it, forming compartments with distinct physiological functions.
“I chose an area of research that would allow me to grow with it,” Schekman said.
In eukaryotic cells, membrane vesicle trafficking is a complex but well-coordinated process where proteins and other cellular cargo are transported by membrane-bound vesicles from one intracellular compartment to another or frequently secreted outside the cell. This transport pathway has important roles in neurotransmission, hormone secretion, and metabolism.
Schekman envisions the cell and its secretory pathway as an ‘assembly line’. “Proteins that are to be secreted are put onto the assembly line by being inserted into or through a membrane called the endoplasmic reticulum. These proteins become covalently modified and packaged into a vesicle, which then moves to another station, where the contents are further modified, and other vesicles are made,” he describes. “It is kind of like an assembly line process with certain rigid steps that can occur very reproducibly.” Schekman’s iBiology lectures are an excellent resource for learning more about this biological phenomenon.
When he was hired as a professor at the University of California, Berkeley, his lab started working on the secretory pathway in baker’s yeast. Yeast is an ideal model organism to apply tools of genetics and biochemistry but was previously not utilized for studying secretion, as the known chemical inhibitors of this pathway did not work in yeast. Schekman and his graduate student Peter Novick, changed their approach and started looking for conditional temperature-sensitive (Ts) mutants instead. In a Ts mutant, a protein is functional at a low temperature but loses function when shifted to a high temperature. The discovery of the first Ts-mutant sec1, defined Schekman’s scientific career.
“The cells under normal conditions have just a small collection of vesicles, but when you block the last step [of secretion] with this mutant sec1, vesicles fill up the cytoplasmic compartment, and eventually the cell chokes because it can no longer grow but it is making all this stuff,” Schekman explains.
“It was the eureka moment in my career to see that electron micrograph image [of sec1 mutant], and I knew from that moment that we would have wonderful experiences over the next 20 years figuring it all out.”
The function of Sec proteins in yeast, discovered by the Schekman lab, is highly conserved and indicates that many genes of fundamental importance in intracellular transport are functionally similar in different organisms. This discovery was recognized with the Nobel Prize in 2013.
Schekman’s contribution to science goes well beyond his research. During the Nobel Prize Inspiration Initiative and other scientific events, Schekman has passionately advocated for academic journal publishing reform. He and other scientists from around the world have signed the Declaration on Research Assessment, urging the scientific community to move away from the use of journal impact factor, a crude assessment of the popularity of a journal.
“Frankly [the high-impact factor] journals are managed by people who are in the business of selling magazines,” he explains. “They are not singularly in the business of promoting scholarship, and I think this is a bad trend.”
According to him, to maintain high-impact factors and appear more selective, many journals frequently reject scientifically-sound research papers and publish manuscripts that are flashy and would be more popular in the scientific community. “Unfortunately, the field has become dominated by commercial interests,” Schekman said. “The most selective journals have a marketing and branding strategy that has captivated the attention of scholars worldwide who desperately try to get their papers published.”
eLife, an open-access scientific journal that promotes collaborative peer review, was born out of Schekman’s desire for change in academic publishing. His lab no longer publishes their research in popular closed-access scientific journals. But unlike established scientists, the ‘publish or perish’ culture in science makes it difficult for early-career researchers to take a similar stand. Schekman confesses that despite his best efforts, many in the scientific community are influenced by “where something gets published rather than what’s in the paper,” but he is hopeful that a change will slowly but eventually happen!
In recent years, Schekman has also promoted collaborative research in academia and is a proponent of academia-industry partnerships. He is also the Scientific Director of Aligning Science Across Parkinson’s, a collaborative endeavor to better understand Parkinson’s disease and develop improved therapeutics.
His advice for early-career researchers is to explore new directions and participate in interdisciplinary research. “In the modern era, the toughest problems require individuals to seek collaborative engagement with other scientists,” Schekman said.“The most successful scientists are people who take risks—nothing ventured, nothing gained.”
The complete video of this interview with Dr. Schekman is available on the YouTube channel of our media partner, ‘Reason with Science’. It is a series of conversations with scientists discussing the importance of science in society. You can listen to the full conversation with Dr. Schekman here:
Author
Sneha Das is pursuing her Ph.D. in Microbiology from the University of Illinois at Urbana-Champaign. She fell in love with the microbial world during her undergraduate education at St. Xavier’s College, Kolkata. Her current research focuses on understanding DNA damage and repair in bacteria using genetic tools. Sneha discovered her passion for science communication as a teaching assistant for undergraduate Molecular Biology and Microbiology courses. Since then, she has talked about different scientific topics to the general audience as a part of science communication outreach programs. In her free time, she enjoys writing, traveling, exploring nature, and meeting new people.
Editors
Ananya Sen is currently a science writer at the Carl R. Woese Institute for Genomic Biology. She completed her Ph.D. in Microbiology at the University of Illinois at Urbana-Champaign in 2021. She is an ardent reader and will happily discuss anything from Jane Austen to Gillian Flynn. Her travel goals include covering all the national parks in the U.S. with her sidekick Oscar, a Schnauzer/Pomeranian mix.
Sumbul Jawed Khan is the Assistant Editor-in-Chief at Club SciWri. She received her Ph. D. from the Indian Institute of Technology Kanpur, where she studied the role of the microenvironment in cancer progression and tumor formation. During her post-doctoral research at the University of Illinois at Urbana-Champaign, she investigated the gene regulatory networks important for tissue regeneration. She is committed to science outreach activities and believes it is essential to inspire young people to apply scientific methods to tackle the challenges faced by humanity. As an editor, she aims to simplify, translate, and excite people about current advances in science.
Illustrator
Andreia Rocha did her M.Sc. at Universidade do Algarve in Faro, Portugal, in Oncobiology and moved to Vienna to complete her thesis at IMBA where she studied stem cells and focused on working with organoids while using them as cancer models. Currently, she is a research assistant at JLP Health, a startup company based in Vienna, Austria. She is also passionate about communicating science through art and illustration and wishes to combine the two careers in the future. You can visit her website and follow her on instagram.
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