Bringing a project to life of the magnitude of the cryoEM facility—which required almost a decade of work and roughly $16 million in total support—required a community of partners, creativity and determined persistence against many obstacles.
Among many crucial UW–Madison collaborators in these endeavors, the Morgridge Institute especially thanks Brian Fox, Elizabeth Wright, Robert Landick and others of the UW–Madison Biochemistry Department; Marisa Otegui of Cellular and Molecular Biology; Richard Moss, senior associate dean of the UW–Madison School of Medicine and Public Health; and Norman Drinkwater, Steven Ackerman, and Cynthia Czajkowski of the Office of the Vice Chancellor for Research and Graduate Education.
These interactions provide a model for how the Morgridge Institute and UW–Madison can partner on transformational science, and it is already inspiring new joint directions.
By Paul Ahlquist, Director, John W. and Jeane M. Rowe Center for Research in Virology
Cryo-EM Data Handling and Processing
Since cryo-EM imaging is inherently computational, this research requires highly advanced data handling and processing. To meet these needs, Morgridge investigators Anthony Gitter, Miron Livny and others recently received UW2020 funding to initiate development of a shared pool of graphical processing units (GPUs) that can greatly accelerate computation for cryo-EM image processing and certain other applications. Further critical work to improve data acquisition, storage, transfer and computation for cryo-EM and other structural biology techniques is being led now by Morgridge scientists Brian Bockelman and Miron Livny.
Complementary EM Capabilities
Growing campus cryo-EM strength was augmented by a successful application to a special HHMI Transformative Technology Competition led by Morgridge Affiliate Marisa Otegui and HHMI investigator Ed Chapman, and formally endorsed by Morgridge and HHMI investigators Phil Newmark and Paul Ahlquist. This $2 million package, funded primarily by HHMI with substantial matching funds from the Morgridge Institute, Medical School and Vice-Chancellor for Research, purchased a 200 kV cryo- and tomography-capable electron microscope being installed in Bock Laboratories, adjacent to Biochemistry. Otegui also led a successful NIH equipment grant for a high-pressure freezer for important types of EM sample preparation. These facilities provide crucial capabilities for cell biology that synergize well with the functions of the new cryo-EM Facility in Biochemistry.
UW Faculty / Morgridge Investigator Hires in Cryo-EM
To balance the new infrastructure, the following faculty were hired through support respectively from the Biochemistry Department, a UW campus faculty cluster hire in molecular virology, and the Morgridge Institute:
Biochemistry Professor and Morgridge Affiliate Elizabeth Wright was recruited from Emory University to lead the new UW Biological CryoEM facility.
Assistant Professor Robert Kirchdoerfer was recruited to a joint Biochemistry – Molecular Virology faculty position to use Cryo-EM to study the structure and function of selected viral assemblies.
Morgridge Investigator and Biochemistry Assistant Professor Timothy Grant was recruited to develop advanced approaches in Cryo-EM image analysis.
New UW Center for Biological Cryo-EM
By mid-2017, pledges by Biochemistry Chair Brian Fox, Morgridge Institute CEO Brad Schwartz, the leadership of the Medical School, and others assured funding for the planned new biological Cryo-EM facility, to be housed in Biochemistry Department space. Key equipment funded included a state-of-the-art Titan Krios automated cryoEM microscope, other cryo-EM microscopes for sample validation, and varied sample preparation equipment.
Cross-Campus Commitment for Major Cryo-EM Expansion
By 2015, discussions among Morgridge Institute and UW Biochemistry Department researchers and other UW stakeholders led to agreement that fuller access to rapidly advancing Cryo-EM capabilities was essential for the campus to remain nationally and internationally competitive in biomedical research. To advance planning and campus awareness, a 2015-16 campus seminar series on The Cryo-EM Revolution brought in Cryo-EM leaders from across the US and Europe. These activities culminated in specific plans for the design, staffing and operation of a new campus facility for biological and biomedical Cryo-EM.
First UW Direct Electron Detector
UW’s cryo-EM capabilities were upgraded by adding a radical new EM camera, a direct electron detector, that increased resolution ten-fold. Morgridge investigator Paul Ahlquist obtained nearly half of the $1 million cost from the Howard Hughes Medical Institute, and led efforts that raised the rest from the Morgridge Institute and UW Biochemistry Department, Medical School, Vice Chancellor for Research and others.
First UW Cryo-Electron Microscope
Bolstered by substantial Morgridge Institute matching funds, a faculty group led by Morgidge Affiliate Marisa Otegui, Morgridge investigators Kevin Eliceiri and Paul Ahlquist and others raised more than $2 million in NSF and other funding for UW’s first cryo-electron microscope. This instrument, sited in the Nanoscale Imaging and Analysis Center, has benefited greatly from College of Engineering operations support.