Medicine Grand Rounds (Edward Rubenstein Lecture): Genes and diseases associated with protein and miRNA secretion (2014 Edward Rubenstein Lectureship)

January 21, 2015 @ 8:00 am – 9:00 am
Li Ka Shing Center for Learning and Knowledge
Stanford University
300 Pasteur Drive, Stanford, CA 94304
Department of Medicine
Medicine Grand Rounds (Edward Rubenstein Lecture): Genes and diseases associated with protein and miRNA secretion (2014 Edward Rubenstein Lectureship) @ Li Ka Shing Center for Learning and Knowledge | Stanford | California | United States

Presenter: Randy Schekman, PhD
Professor of Cell and Developmental Biology
University of California, Berkeley

Dr. Randy Schekman is a Professor in the Department of Molecular and Cell Biology, University of California, Berkeley, and an Investigator of the Howard Hughes Medical Institute. He studied the enzymology of DNA replication as a graduate student with Arthur Kornberg at Stanford University. His current interest in cellular membranes developed during a postdoctoral period with S. J. Singer at the University of California, San Diego. At Berkeley, he developed a genetic and biochemical approach to the study of eukaryotic membrane traffic. Schekman has been awarded honorary doctorate degrees from the University of Geneva and the University of Regensburg. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. From 2006-2011, he was Editor-in-Chief of the Proceeding of the NAS. Currently he is Editor-in-Chief of the open access journal eLife. He is also the Editor-in-Chief of the Annual Reviews of Cell and Developmental Biology. Dr. Schekman was Head of Faculty for Cell Biology for F1000, the Scientific Director of the Jane Coffin Childs Fund (ended 2012), and Chair of the Scientific Advisory Board of the Tamasek Life Science laboratory, Singapore (ended 2012).  He was also the Editor-in-Chief of the Proceedings of the National Academy of Sciences (until 2011), and was an elected Council member of the American Academy of Arts and Sciences (until this year).

Among his awards are the Eli Lilly Award in microbiology and immunology, the Lewis S. Rosenstiel Award in basic biomedical science, the Gairdner International Award, the Amgen Award of the Protein Society, the Albert Lasker Award in Basic Medical Research and the Louisa Gross Horwitz Prize of Columbia University. In 2013, Schekman was awarded the Nobel Prize in Medicine or Physiology jointly with Thomas Südhof and James Rothman for their contributions to understanding vesicle trafficking.

Dr. Schekman was recently awarded the 2013 Nobel Prize in Physiology or Medicine and shared this award with James Rothman and Thomas Südhof for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells. His work concerns the mechanism of membrane assembly and vesicular traffic in eukaryotic cells. What Schekman, using genetic methods, and Rothman, with biochemical approaches, working independently did, was dissect in meticulous detail the molecular underpinnings behind vesicle formation, selection of cargo, and movement to the correct organelle or path outside the cell.

Dr. Randy and his laboratory identified 50 genes involved in vesicle movement and determined the order and role each of the different genes’ protein products play, step by step, as they shuttle cargo-laden vesicles in the cell. One of the most important genes he found, Schekman says, is the SEC61 gene, which encodes a channel through which secretory proteins under construction pass into the endoplasmic reticulum lumen. When this gene is mutant, proteins fail to enter the secretion assembly line. Another significant set of genes he discovered encode different coat proteins that allow vesicle movement from the endoplasmic reticulum and from the Golgi.

Although Schekman’s research was done in yeast, follow-up studies confirmed that higher organisms, such as humans, share the majority of the genes in the yeast secretory pathway. Such knowledge provided a foundation for understanding normal human cell biology and disease states. In fact, as the study of the genetics of mammalian cells has become easier, Schekman has been characterizing human diseases that arise from secretory pathway problems. He has identified the structural basis of a rare craniofacial disease that disrupts the construction of a coat protein complex essential for transport vesicle formation. He also is studying whether the accumulation in the brains of Alzheimer’s disease patients of the protein amyloid is due to a secretion pathway roadblock.

While many steps in vesicular trafficking are now known, some have evaded discovery. Schekman continues to look for receptors in the endoplasmic reticulum membrane that find appropriate protein cargo for transport to the Golgi. He is also trying to identify molecules that help protein-laden vesicles move from the Golgi out of the cell. Schekman, with as much passion for science today as he has had throughout his career, is confident he can persuade Nature to reveal undiscovered routes in her traffic patterns.