From the Deputy Director for Intramural Research

Seeing Is Believing

BY MICHAEL GOTTESMAN, DDIR

Neuroscientists tell us that a large percentage of the information received and processed by the human brain comes through the visual system. It should come as no surprise then that many advances in biological science have resulted from improvements in how instrumentation helps us perceive the physical world, and that advances in data processing have often coincided with improvements in the visual display of information. Microscopy, in particular, has allowed increasing resolution of biological structures, and data processing of increasingly complex datasets has resulted in striking images at the molecular and atomic levels that enhance our understanding of biological events.

The intramural program has always been at the leading edge of developing new approaches to visualize biological phenomena, and some recent investments highlight our desire to remain at the cutting edge. In this brief essay, I will update you on some of the trans-NIH initiatives that illustrate this point.

This issue of the NIH Catalyst describes the Advanced Imaging Microscopy (AIM) core, run by Hari Shroff (NIBIB). It’s a trans-NIH shared resource—available for use by the entire NIH intramural community—that houses, operates, disseminates, and improves noncommercial, prototype optical-imaging systems developed at NIH. (The AIM story begins here.)

In addition, you are undoubtedly aware of the recent revolution in cryo-electron microscopy that has allowed true atomic resolution of purified protein preparations. This technology, which was originally developed in part by Sriram Subramaniam (formerly at NCI), is now entering more routine use to analyze structures of membrane proteins, protein complexes, and many other difficult-to-crystallize proteins. There are three consortia that have pooled resources to enhance access to these technologies by many more scientists at the NIH. The first, known as MICEF—short for Multi-Institute Cryo-Electron Microscopy (EM) Facility—includes staff from NIDDK, NHLBI, NINDS, and NIAMS who receive support in planning EM experiments, preparing samples, imaging, using equipment, and analyzing data. The MICEF has a new Titan Krios high-resolution electron microscope and a screening electron microscope and other state-of-the-art equipment. This past year, we also established the NIH Intramural Cryo-EM facility (NICE), which has another Titan Krios donated by NCI with research support similar to MICEF, and contributions from NCI, NICHD, NIAID (which has an additional Titan Krios at Rocky Mountain Laboratories in Hamilton, Montana), and NIEHS. The MICEF and NICE consortia are being overseen by NICE Director Jenny Hinshaw (NIDDK). The goal is, as equipment comes online, to create a shared facility for use by all intramural scientists.

Another emerging EM molecular-visualization technology is known as cryo-focused ion beam or cryo-FIB. This technique allows the resolution at the molecular level of structures within frozen sections of biological samples such as cells. In its ultimate manifestation, cryo-FIB would allow identification of molecules and molecular assemblies within cellular structures. For cell biologists, this is the final frontier. Several institutes, including NHLBI, NINDS, NIAMS, and NIDDK, are forming a consortium to recruit scientists whose goal will be to develop this technology at the NIH. Space and equipment to begin this enterprise have been identified. There will be more to come.

Finally, I want to remind you about the recent acquisition of a lattice light sheet microscope from Zeiss that will be housed in a facility in NHLBI. Clare Waterman and Xufeng Wu will oversee the management of this equipment, which projects ultrathin, low-intensity planes of light into a biological sample and boosts image clarity while reducing phototoxicity and photobleaching. The equipment will allow researchers to image live cells and tissues at high resolution and in 3-D for extended periods. There is a user’s committee that will determine priority for use, so please let Dr. Wu know of your interest (wux@nhlbi.nih.gov).

And, of course, NIH now has a database of cores, called CREx, that can help you solve any of a myriad of research problems, including the need for high-resolution light and EM imaging. For resources, click here. Don’t forget to check with CREx to find the help that you need (you just need your NIH user name and password to access it).