In 1972, the Rosenstiel Center and the three science departments hired Susan Lowey (Biochemistry), Carolyn Cohen (Biology), and Donald Caspar (Physics). During the moving in, Caspar coined the term ‘structural biology’ as a more accurate description of their goal, compared to the in-vogue term ‘molecular biology’. The three faculty were housed on the Rosenstiel fourth floor, which they named The Laboratory of Structural Biology. The aim of the group was structural studies of large complexes: muscle and viruses. In 1973, David DeRosier (Physics) joined the other three. Caspar studied muscle and viruses, Cohen and Lowey studied muscle, and DeRosier studied actin and bacterial flagella. The group utilized both x-ray diffraction and electron microscopy (EM). In addition to an x-ray diffraction suite, they set up an EM suite, which had rooms for two microscopes with a darkroom between them. The antechamber had space for negative staining and carbon coating of grids. The first microscope was a Philips EM 301, which was the state of the art at that time.
During the first ten years, the facility was overseen by Paul Norton, who was an experienced electron microscopist. Paul left after 10 years and for a brief interim, the facility was managed by Hal McKeel. When McKeel left in 1984, Linda Melanson, also an experienced electron microscopist, was hired. On her arrival, the group had obtained funds to purchase a second EM, a Phillips 420, which was equipped with a low-dose controller. It occupied the second EM room on the 4th floor. Both microscopes sat on anti-vibration platforms to minimize the vibrations on the floor. The anti-vibration platform worked well if no one touched the microscope, but on these models, the shutter button was on the microscope column. It was not ideal.
In 1987, Hugh Huxley joined the Rosenstiel and began using the EMs to study muscle. Shortly after his arrival, the group decided to buy an improved, computer-controlled, low-dose microscope, the Philips CM12, but wanted to put it on the ground floor to eliminate the need for an anti-vibration platform. The group was given space for two adjacent rooms on the ground floor of Rosenstiel. One was used for the 420, and the other for the CM12. Following the lead of Unwin and Henderson at the MRC-LMB, the group built a gravity-fed water cooling system, which eliminated the water pressure fluctuations generated by a standard water chiller. The water in the chiller was pumped into a tank on the penthouse (7th floor), maintaining a level by pumping more water than needed into the tank, while the overflow returned to the chiller directly. The water for the microscope flowed out from the bottom of the tank and through the microscopes. The two rooms and antechamber were sealed from the rest of the building and had their own air conditioner and air dryer. The humidity had to be kept below 20% to prevent ice contamination on the frozen-hydrated EM grids as they were transferred into the microscope. Across the hall from the EM suite was a utility closet, which housed the chiller and a men’s bathroom; it was converted into a darkroom to handle EM films.
In 1999, Niko Grigorieff joined the Rosenstiel Center and began work on single particle cryo-EM. Funds for a higher resolution 300keV, FEG cryo-microscope were obtained from several sources, including the NSF and HHMI. The University agreed to remodel the first floor of the Rosenstiel to house the new microscope. The air conditioner and air drying systems were housed in a separate room attached to the outer wall of the Rosenstiel. In 2001, Linda Melanson left the group, and Chen Xu was hired to manage the EM facility. Grigorieff and DeRosier partnered with Tom Walz and Steve Harrison to obtain a program project grant, which paid for maintenance on the EM. In 2006, Dany Nicastro joined the Rosenstiel and began to perform cryo-electron tomography on eukaryotic flagella. In 2010, the group replaced the 420 (120keV, LaB6) with an F20 (200 keV with a FEG). A Falcon direct electron detector is now attached to the F30.
Where are they now:
- In 1994, Dr. Caspar left to join the faculty at Florida State University.
- In 1997, Dr. Huxley retired. He died in 2013.
- In 1998, Dr. Lowey left to join the faculty at the University of Vermont.
- In 2005, Dr. DeRosier retired.
- In 2012, Dr. Cohen retired. She died in 2017.
- In 2013, Dr. Grigorieff left to join Janelia Farm.
- In 2015, Dr. Nicastro left to join the faculty at The University of Texas Southwestern Medical Center.
- In 2016, Dr. Chen Xu left to join U Mass Medical School.
In 2017, Professors Bruce Goode and Avital Rodal took over management of the facility, with generous support from the University. The facility is now run by Mike Rigney, who worked with Grigorieff from 2001-2015. The EM facility is available, at competitive hourly or daily rates, to Brandeis users, outside academic users, and for-profit users.