Yonsei Advanced Science Institute

Seminar and lunch session with Randy Schekman at Yonsei University

ON OCTOBER 5, Yonsei-IBS Institute held “The Challenge Toward the Dream of Nobel Laureate” seminar where Randy Schekman, cell biologist, professor of Molecular & Cell Biology at the University of California, Berkeley, and the recipient of the 2013 Medicine and Physiology Nobel Prize, shared his journey of rigorous research into the cell secretion of proteins.

Attending the seminar session at IBS

   In the seminar, Schekman introduced the breakthrough research that brought him his Nobel Prize, as well as the current research being conducted on cellular transport. In biological cells, proteins to be secreted outside of the cell go through a conveyor belt-like arrangement of membranes where they are trafficked from the endoplasmic reticulum, the site of synthesis, through the Golgi apparatus. Finally, cell vesicles—small, enclosed sacs—transport the secretory proteins to fuse with the plasma membrane[1], allowing for discharge to the cell exterior. Schekman embarked on his research into this secretion process in 1976 when the vesicle transport process at the molecular level was still largely unknown. He chose to study baker’s yeast, Saccharomyces cerevisiae, a unicellular organism with a simple structure. Yeast cells divide through a process called “budding,” which involves the fusion of vesicles. These vesicles are responsible for the secretion of enzymes[2] used in the budding process, as well as for the formation of essential building blocks of the cell membrane. In his study, Schekman explored temperature-sensitive gene mutations that hinder the excretion of vesicles and the consequent growth of yeast cells. By warming cells up to a temperature of 37°C, vesicles could not escape the cell, thus building up in the cytoplasm. Through this process, more than 200 mutations could be isolated along with the genes responsible for the various stages of the yeast cells’ secretory pathway. The findings on vesicle transport have diverse applications, such as in the biotechnology industry, where yeast cells are engineered and cultured in factories to produce human recombinant insulin[3] at reduced costs. Moreover, yeast cells are able to be utilized in the production of the protein used in Hepatitis B vaccines.

   Schekman’s recent works have been an extended effort to further explore cell vesicles. For instance, he has conducted research into exosomes[4], which can carry RNA molecules to target cells in order to induce changes in gene expression or to promote a pathological process. He hopes that the current studies into the assembly of exosomes can be applied to deliver therapeutic molecules to cells or tissues.

Sharing his experience

   The Yonsei Annals attended a lunch mentoring session with Professor Schekman held upon the completion of the seminar to gain further insight into his career, and to receive advice for aspiring students wishing to develop their careers in the field of biological sciences.

CONTRIBUTE BY CHOI GO-EUN

   Annals: Could you provide the most valuable experience from your college years that has shaped your career in research?

Schekman: Even before college, I had been deeply interested in microorganisms. When I entered the University of California, Los Angeles (UCLA), I began my academic career with the intention of going to medical school. However, my experience in the research laboratory as a freshman redirected my goals. In my first year of chemistry class, I was put in an Honors course taught by Willard Libby, a Nobel Laureate who invented Carbon-14 dating[5]. It offered a special experience, where every student got to choose a laboratory from the Chemistry department to work for 10 weeks. The professor of the lab gave me the first edition of The Molecular Biology of the Gene written by James Watson. Reading this book was thrilling and exciting as it described molecular biology in a way that no other textbook could, inspiring me to pursue experimental science. I continued lab work in my second year on viral DNA replication and published several papers, then eventually got admitted to the lab of Arthur Kornberg, the most prominent biochemist at that time. There is no way of finding out whether you are genuinely interested in a research career until you actually try it. Therefore, I strongly recommend experiencing hands-on laboratory work as it allows you to engage in real science and cutting-edge work that expands beyond your typical coursework.

 Annals: Generally speaking, accomplishing breakthroughs and widely recognized discoveries takes a very long time in the field of biomedical science. What kind of attitude should researchers have in order to endure challenges and uncertainties during this arduous journey?

Schekman: Regarding my research—despite encountering some difficulties—I believe I was fortunate that things worked out relatively smoothly. However, I initially struggled to secure research funds when completing my postdoctoral research on biological membranes. Although I knew I wanted to study cell membranes and was aware that I had a comparative advantage of using baker's yeast to study the process, I did not necessarily have the professional credibility to conduct research in this field, as I had no prior experience with yeast cells or genetics, and did not have any preliminary results to show. The first request to the National Institute of Health (NIH) for a grant was rejected, and my research was regarded as naive and risky. However, once I began my research and discovered the first mutation, “Sec 1,” I knew I was working on something extraordinary—something that was worth at least 20 years of research to completely apprehend.

   Generally, experiments do not work most of the time, and many researchers are forced to face failures and frustrations on the daily. Something I learned in graduate school is that after you have found a topic worthy of exploration, you need to focus on it with persistent intensity. Smart individuals have many ideas, and new ideas can often divert their attention—they often become too distracted and end up wasting time. Additionally, it is important to step out of your comfort zone and explore uncharted territories. Many people tend to be conservative and feel uncomfortable starting something new and different. My advice for aspiring researchers would thus be to try developing a unique and irreplaceable identity that separates you from the rest of the group.

    Annals: In South Korea, many students genuinely interested in basic sciences are reluctant to choose biomedical sciences or biology as their majors due to the widespread understanding that it is not a lucrative career. What do you think about this phenomenon?

Schekman: It is not necessarily true that researchers are financially insecure. Of course, I would not have said so with certainty when I started my career as that was before the biotechnology industry began thriving. However, I think the financial equation has changed now: I see most graduates enter the biotechnology field and attain financially stable jobs. Students can also do extremely well if their startup succeeds. Therefore, I do not think you should make a career choice based on economic benefits.

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   The seminar and the lunch mentoring session lent valuable insight into Schekman’s groundbreaking work in the field of cell biology. The Annals was able to learn about his life as a passionate researcher who pursued his vision for decades and has—as a result—led critical discoveries which are being directly applied to treat patients in the clinical setting.

[1] Plasma membrane: A biological membrane that separates the interior of the cell from the outside environment
[2] Enzymes: Proteins that catalyze biochemical reactions
[3] Recombinant insulin: Insulin derived from non-human cells which mimic human insulin
[4] Exosome: An extracellular vesicle that carries signaling molecules, nucleic acids, and lipids without direct cell-to-cell contact, enabling intercellular communication
[5] Carbon-14 dating: A method of determining the age of an organic material by measuring the content of a radioactive isotope of carbon, carbon-14