Chan Zuckerberg Institute for Advanced Biological Imaging

To cure, prevent, or manage all diseases by the end of the century, we need to develop a dynamic, integrated view of biological systems in health and disease. To accomplish this goal, the Chan Zuckerberg Initiative is creating a new advanced biological imaging institute. Located in California’s Bay Area, disciplines will come together to develop revolutionary new imaging hardware and software tools that provide comprehensive views of biological systems in their native context.

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The inner workings of an algal cell as depicted with cryo-electron tomography, which aggregates multiple snapshots of a single piece of material. Visible are the endoplasmic reticulum (yellow), Golgi apparatus (green and magenta), and vesicles (multi-colored circles). | Photograph by Y. S. Bykkov et al./eLIFE (CC BY 4.0)
The inner workings of an algal cell as depicted with cryo-electron tomography, which aggregates multiple snapshots of a single piece of material. Visible are the endoplasmic reticulum (yellow), Golgi apparatus (green and magenta), and vesicles (multi-colored circles). | Photograph by Y. S. Bykkov et al./eLIFE (CC BY 4.0)

A Multimodal, Multidisciplinary, Systems Engineering Approach to Technology Development

The Chan Zuckerberg Institute for Advanced Biological Imaging (CZ Imaging Institute) aims to push forward the development and application of new imaging technologies over the next 15 years to obtain deep insights into the architecture of complex biological systems at the molecular level. Researchers will collaboratively develop breakthrough biological imaging systems centered around grand challenges that push the boundaries of what we can see and measure.

The CZ Imaging Institute will bring together scientists, software and hardware engineers, and application specialists with collective expertise in artificial intelligence, physics, probe development, tool development, biomedical engineering, and biological applications to develop breakthrough integrative and multimodal biological imaging systems. The technologies developed will be driven by the needs of the research biology community, broadly disseminated, and ultimately refined for applications beneficial to human health.”
Mark Zuckerberg, Co-Founder and Co-CEO, Chan Zuckerberg Initiative

As an extension of the CZI Imaging program, the institute will ensure broad access to new technologies through a visiting scientist program and disseminate tools to benefit the entire imaging field. The institute will create technologies — hardware, software, biological probes, data, and platforms that will be made available to the scientific community and adopted worldwide through a combination of direct access to the institute, open sharing of advances, and commercial partnerships.

Initial Scientific Focus: Developing Technologies to Map Proteins in Cells

Building on the progress of CZI’s Visual Proteomics grant program, the initial scientific focus of the CZ Imaging Institute is to develop technologies and methodologies to image the molecular architecture of the cell with atomic resolution. Our goal is to make it practical to view any desired cellular complex, structure or organelle at the highest possible resolution and to understand these structures in a broader biological context.

We can now visualize the structure of proteins at high resolution by averaging the images of hundreds of thousands or millions of individual, purified protein molecules using single-particle cryo-electron microscopy. We can also visualize organelles and very large complexes in the cell using cryo-electron tomography. Between predictions of individual protein structures by machine learning methods such as AlphaFold2 and RoseTTAFold and their increasingly rapid experimental validation and correction via single-particle cryoEM, understanding the structures of individual molecular components of the cell is a nearly solved problem. The challenge then is to determine how these parts come together and the consequences of often weak and dynamic associations that only play out in an intact cell, but are critical for proper cell function.

Observing any biological process inside the cell requires imaging technologies that provide molecular specificity — seeing particular biological macromolecules, metabolites, and comprehensive molecular coverage — with the ability to simultaneously see all the molecules involved in the process.

Already, a number of very promising technological approaches for comprehensive, macromolecular imaging at the molecular resolution length scale, are being funded through the CZI’s Visual Proteomics Frontiers grant program. Future Frontiers grant programs will continue to invest in promising technological approaches focused on Dynamic Imaging.

Scientific Leadership: Meet our Founding Members

David Agard
  • Founding Scientific Director
  • Professor, Departments of Biochemistry & Biophysics and Pharmaceutical Chemistry,
  • University of California, San Francisco
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David A. Agard, Ph.D. is a Professor of Biochemistry and Biophysics at the University of California, San Francisco. His current research focuses on elucidating the mechanism of cytosolic protein homeostasis as driven by the Hsp90 and Hsp70 molecular chaperones and their roles in human health and disease. Additional areas focus on the structure and organization of centrosomes, basal bodies, and cilia, and the structure and complex cell biology of the nuclear compartment encoded by jumbo bacteriophage. Accompanying this is a continuing effort to develop new technologies for high-resolution cryoEM and cryoET.

David was the founding Director and subsequently, a Scientific Director of the multi-campus Institute for Bioengineering, Biotechnology, and Quantitative Biomedical Research between 2001–2006 and was a Howard Hughes Medical Institute (HHMI) Investigator from 1986-to 2019. He earned his B.S. in Molecular Biochemistry and Biophysics from Yale University and his Ph.D. in biological chemistry from the California Institute of Technology and did his postdoc at the MRC Laboratory of Molecular Biology in Cambridge, England. David was elected to the National Academy of Sciences in 2007 and the American Academy of Arts and Sciences in 2009.

Bridget Carragher
  • Founding Technical Director
  • Co-Director, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY
  • Adjunct Professor, Columbia University, New York, NY
  • Founder and Chief Technology Officer, NanoImaging Services, Inc.
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Bridget Carragher received her Ph.D. in Biophysics from the University of Chicago in 1987. She then worked in various positions, both in industry and academia, until moving to the Scripps Research Institute in 2001. From 2002–2022, together with Clint Potter, she served as the Director of the National Resource for Automated Molecular Microscopy (NRAMM), an NIH-funded national biotechnology research resource. NRAMM’s mission was the development of automated imaging techniques for solving three-dimensional structures of macromolecular complexes using cryo-transmission electron microscopy (cryoEM). NRAMM contributed a number of novel technical advances for cryoEM and cryoET and has been acknowledged in more than 470 scientific publications.

In 2007 Bridget and Clint co-founded NanoImaging Services, Inc., which provides cryoEM and other microscopy services to the biopharmaceutical and biotechnology industry. In 2015 Bridget and Clint moved their academic lab from The Scripps Research Institute to the New York Structural Biology Center and took up positions as Co-Directors of the Simons Electron Microscopy Center (SEMC). SEMC has since expanded to encompass the National Center for CryoEM Access and Training, the National Center for In-situ Tomographic Ultramicroscopy, and the Simons Machine Learning Center. Bridget is also an Adjunct Professor at Columbia University, BMB department.

Clint Potter
  • Founding Technical Director
  • Co-Director, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY
  • Adjunct Professor, Columbia University, New York, NY
  • Founder and Chief Technology Officer, NanoImaging Services, Inc.
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For 30 years, Clint Potter has focused his career on developing and managing the application of computational technologies to imaging systems with applications including satellite reconnaissance systems, medical imaging, and structural biology. For the past 25 years, in collaboration with Bridget Carragher, Clint has focused on the development of technology for advancing electron microscopy methods for structural biology through automation with a focus on single-particle cryoEM and cryo-electron tomography. These projects have covered all aspects of the pipeline including grid substrate development and improved vitrification devices and developing automation software for data collection and processing.

Clint has extensive experience designing, building, managing, and running microscopy facilities and negotiating the purchase, installation, and successful operation of high-end instruments. To date, Clint has managed the purchase and installation of 10 FEI Titan Krios microscopes. He currently serves as Co-Director of the Simons Electron Microscopy Center, the National Center for CryoEM Access and Training, the National Center for In-situ Tomographic Ultramicroscopy, and the Simons Machine Learning Center. Clint is also an Adjunct Professor at Columbia University, BMB department.

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