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Tackling the Central Dogma with an Optical Trap
Jamais Cascio, 15 Nov 05

image courtesy Stanford UniversityStanford researchers have designed the first microscope sensitive enough to watch a protein molecule function in real time -- and in doing so, they may have both solved some of the deepest questions about how DNA replicates and kicked off an entirely new field of study.

Dr. Steven Block and his team designed and built an "optical trap" microscope that uses the minute pressure of infrared light to hold a molecule in place for measurement without interfering in how the molecule works; the system has an accuracy of one angstrom, equal to one-tenth of a nanometer -- roughly the diameter of a single hydrogen atom. This allowed them to watch genes being copied in real time. And this, in turn, let them resolve a question at the heart of what biologists call the "central dogma."

They published two nearly-simultaneous articles on their work, one in the in the November 11 edition of Physical Review Letters, discussing the microscope, and the other in the November 13 advance publication of Nature, addressing their findings:

In the Nature study, Block and his colleagues tackled a fundamental principle of biology known as the central dogma, which states that in living organisms, genetic information flows from DNA to RNA to proteins. [...]

The Block team focused on a crucial step in the central dogma, a process known as "transcription," where each gene is copied from DNA onto RNA.

Transcription begins when an enzyme called RNA polymerase (RNAP) latches onto the DNA ladder and pulls a small section apart lengthwise. The RNAP enzyme then builds a new, complementary strand of RNA by chemically copying each base in one of the exposed DNA strands. RNAP continues moving down the DNA strand until the gene is fully copied. [...]

Exactly how transcription works at the molecular level has been intensely debated among scientists.

What they found was that neither of the two prevalent theories, proposing different mechanisms for RNAP to read DNA in "chunks," was correct. Instead, an older idea, that RNAP simply climbs DNA like a ladder, one rung at a time, appears to be the right one.

The most immediately-useful application of the microscope was demonstrated by their observation of protein folding mechanisms. Misfolded proteins (sometimes called prions) are thought to be at the root of a number of very nasty diseases, including Alzheimer's, Mad Cow, and Parkinson's. A better understanding of how proteins fold -- and sometimes fold incorrectly -- could be crucial for treating or even preventing these diseases.

But this technology can do more than resolve some existing biological questions; it may well kick off entirely new fields of study and application.

"If I look in my crystal ball and see where this is going, I think this blows open the field of single-molecule biophysics," Block says. "We have achieved a resolution for a single molecule comparable to what a crystallographer typically achieves in a millimeter-sized crystal, which has 1,000 trillion molecules in it. Not only are we doing all this with one molecule at 1-angstrom resolution, we're doing it in real time while the molecule is moving at room temperature in an aqueous solution."

As this suggests, the the longer-term implications beyond better understanding of protein folding are a bit less clear, but heavy with potential. This new tool enables us to learn how biological mechanisms work at an unmatched scale and resolution, a scale where effects previously only of concern to physicists start to come into play. It could allow us for the first time to explore deeper questions about how we function at the scale of the atom.

Quantum biomechanics, anyone?

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Comments

That is some *serious* coolness, and geekalicious too.

Central Dogma!

*BRRRRRRRR...shivers and trolls off to the Wikipedia*


Posted by: Rohit Gupta on 15 Nov 05

I don't think this gets us to quantum-scale as per the last comment. But it is likely to tell us some pretty helpful things.


Posted by: Andii Bowsher on 16 Nov 05

Wow!


Posted by: Jesse Jenkins on 16 Nov 05

The "quantum biomechanics" was a bit of a hand-wave, but quantum effects do start to show up when working at the scale of a single atom. This gets us pretty damn close to that scenario.


Posted by: Jamais Cascio on 16 Nov 05

This thing will certainly help to experimentally test various mathematical models of the protein folding problem.

And I think it will make a big difference for a bright green future. A lot of toxic waste is generated in industrial chemistry because of inefficient catalysts. This optical trap microscope may help us to find, test or even build better catalysts. If it can do that, the ramifications are enormous--better fuel cells, cleaner distilling of petroleum and coal, better bio-remediation and so on.


Posted by: Pace Arko on 16 Nov 05



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