Heads of Laboratories
Investigator, Howard Hughes Medical Institute
John D. Rockefeller Jr. Professor
Laboratory of Cell Biology
The nuclear pore complex (NPC), the cell’s largest and most versatile transport channel, controls the traffic of molecules into and out of the nucleus. The Blobel lab discovered the first protein components of this sophisticated portal and has proposed that it opens and closes via a dynamic cycle. Currently, the group is studying the structure of the NPC at the atomic level and the process by which it is assembled.
Blobel, a Rockefeller head of laboratory for 51 years, died February 18, 2018. Read more here.
The nuclear envelop of every eukaryotic cell is speckled with at least one thousand octagonal NPCs, each weighing 100 million Daltons, a massive size by molecular standards. The Blobel laboratory investigates the atomic architecture of these large, complex structures, and the means by which they control traffic into and out of the nucleus, the sanctuary in which the cell houses its chromatin.
The NPC was first identified and described in the 1950s by Michael Watson, working in the Rockefeller University laboratory of Keith Porter and George Palade. Two decades later, Blobel began investigating these cellular structures at the molecular level. The first protein components of the NPC were described in his lab and dubbed nucleoporins, or “nups.” Each of the approximately 30 distinct nups now identified is present in at least eight copies, but most at 16, generating an eight-fold symmetry. Members of Blobel’s lab have also isolated and characterized the first transport factors that chaperone cargo into and out of the nucleus, and identified their binding sites on nups.
In 2004, the Blobel lab set out to piece together the structure of the NPC at the atomic level using X-ray crystallography. The group began examining the ordered regions of nups, and found evidence of dynamic interactions among these proteins. In particular, snapshots of Nup54 and Nup58 led Blobel to propose that the NPC opens and closes via a “ring cycle.”
During this cycle, the NPC’s midplane ring transits between a closed conformation, characterized by three small rings, each containing solely Nup58 or Nup54, and an open conformation, in which Nup58 and Nup54 associate to form a single large ring with a diameter of about 40 nanometers. Recent biophysical experiments suggest that transport factors act as ligands, prompting the ring to open. When a factor known as karyopherin binds to the disordered regions of Nup58, it stabilizes the protein in such a way that the dilated conformation becomes more energetically favorable. While the NPC is sometimes conceptualized as a rigid tube with a gel-like barrier, these experiments show it in fact has a dynamic, flexible structure. Ongoing studies continue to define NPC architecture at an atomic level.
Another major focus of the lab is to study the assembly of the NPC, a process that starts with the formation of a pore through the nuclear envelope. The lab is testing the hypothesis that distinct membrane proteins associate with nups to prompt the fusion of the nuclear envelope’s inner and outer membranes. According to this model, the pore is formed as the nups fill it.
The Blobel lab is also interested in other inputs necessary for NPC formation. The role of chromatin is of particular interest, as NPCs appear to orient themselves in relation to chromosomes, but the mechanism by which this happens is not yet known.
University of Tübingen
Ph.D. in oncology, 1967
University of Wisconsin, Madison
The Rockefeller University, 1967–1969
Assistant Professor, 1969–1973
Associate Professor, 1973–1976
The Rockefeller University
Howard Hughes Medical Institute
U.S. Steel Award, 1978
Canada Gairdner International Award, 1982
Warburg Medal, German Biochemical Society, 1983
Richard Lounsbery Award, 1983
V.D. Mattia Award, 1986
Wilson Medal, American Society for Cell Biology, 1986
Louisa Gross Horwitz Prize, 1989
Albert Lasker Basic Medical Research Award, 1993
King Faisal International Prize, 1996
New York City Mayor’s Award for Excellence in Science and Technology, 1997
Massry Prize, 1999
Nobel Prize in Physiology or Medicine, 1999
National Academy of Sciences
American Philosophical Society
Pontifical Academy of Sciences
German Order of Merit
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