Steven M. Block, a professor of biological sciences and of applied physics at Stanford University, and his team have developed two-dimensional optical force clamps that can monitor the action of a single RNA polymerase (RNAP) enzyme.
In a new study in the journal Nature, Block and his colleagues present strong evidence to support this proofreading hypothesis. Their results -- based on actual observations of individual molecules of RNAP -- are posted on Nature's website: http://www.nature.com. In another set of experiments published in the Nov. 14 issue of Cell magazine, the researchers discovered that RNAP makes thousands of brief pauses as it pries open and copies the DNA double helix.
"Together these two papers push the study of single proteins to new limits," Block said. "We've been able to achieve a resolution of three angstroms -- the width of three hydrogen atoms -- in our measurements of the progress of this enzyme along DNA. In so doing, we've been able to visualize a backtracking motion of just five bases that accompanies RNAP error-correction or proofreading."
Both studies were conducted using two-dimensional optical force clamps -- unique instruments designed and built by the Block lab. Located in soundproofed and temperature-controlled rooms in the basement of Stanford's Herrin labs, these devices allow researchers to trap a single molecule of RNAP in a beam of infrared light, and then watch in real time as it moves along a single molecule of DNA.
"We've been able to reduce drift and noise in our instruments to such an extent that we can see the tiniest motions of these molecules, through distances that are less than their own diameters," Block explained. "Studying one macromolecule at a time, you learn so much more about its properties, but these kinds of experiments were just pipedreams 15 years ago."
This is an example of why the rate of advance in biological science is not constant. The development of instrumentation that can study components of biological systems down on the scale at which they operate will allow these systems to be figured out orders of magnitude more quickly. The biggest reason we still know only a small fraction of what there is to understand about cells and diseases is that we can't watch what happens down at the level at which events actually take place. Continued advances in the ability to build smaller devices and smaller sensors will make observable that which it has previously never been possible to observe.
|Share |||Randall Parker, 2003 December 08 07:06 PM Biotech Advance Rates|