$4 million to aid understanding of cells

Caltech is the birthplace of structural biology, which was invented by Linus Pauling in the 1940s. Unwilling to rest on its laurels, the Institute will seek out new frontiers in the field with the help of a $4 million grant from the Gordon and Betty Moore Foundation. The grant will be used to create a state-of-the-art cryoelectron microscopy laboratory.

Structural biology research at Caltech continues today in the Pauling tradition, using information obtained from high-resolution structures to understand the molecular basis of biological processes.

“Caltech is committed to making every effort to give our faculty the tools they need to be productive,” says Caltech president David Baltimore. “This equipment will enable our researchers to push beyond current understandings of intra-cellular activity to gain a more complete understanding of the life cycle of a cell, which is critical to understanding intercellular dynamics and larger organic systems.”

The future of structural biology lies in bridging the microscopic resolution between the atomic scale (accessible through X-ray crystallography and nuclear magnetic resonance spectroscopy) and the domain above 0.5 microns that is accessible via optical microscopy.

Through cryoelectron microscopes, the tiny “specks” that make up a cell’s machinery for manipulating DNA, mak-ing protein molecules, and interacting with the outside world come into focus. While the field has been around for more than two decades, today’s cryoelectron microscopy and its computational methods are undergoing a revolution that allows new sorts of analyses and much-higher-resolution images, bordering on the low-resolution limits of X-ray crystallographic structures.

With the grant, Caltech will be able to purchase two cryoelectron microscopes capable of imaging biological material in an essentially native state. The first cools the sample material to liquid-nitrogen temperatures and will be used for rapid specimen screening. The second cools the samples to liquid-helium temperatures (near absolute zero), and is in several respects a true prototype expected to deliver images of a higher resolution than has ever before been obtainable.

One of the key microscope users will be Assistant Professor of Biology Grant Jensen, whose goal is to extend traditional structural biology to a cellular level in order to allow realistic computer simulations of whole cells in the future. This work can be thought of as a logical next step after sequencing genomes because it aims to reveal how the various gene products come together to form protein “machines,” and how those machines arrange themselves into the biochemical “assembly lines” that create life.

Formed in 2000 by Gordon and Betty Moore, the Moore Foundation aims to improve the quality of life for future generations. Gordon Moore received his PhD in chemistry from Caltech in 1954 and later founded the Intel Corporation. The foundation focuses on higher education, scientific research, the environment, and select San Francisco Bay–area projects. Its largest commitment to date has been a pledge to Caltech of $300 million, of which this grant is a portion.