WC Archive

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?