September 8, 2003

New Method to Examine Proteins

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Michelle D. Wang and Steven J. Koch of Cornell’s department of physics published an article this past July in the journal Physical Review Letters that mapped out a new and innovative method for examining the proteins in living cells that interact with DNA.

As genetics has taken its place on the forefront of scientific technology, this new finding proves especially significant: it is these molecules that allow the information stored on the DNA strands to be translated for use within an organism.

The article, titled “Dynamic Force Spectroscopy of Protein-DNA Interactions by Unzipping DNA”, explains the process of this new technique, which combines two previously known techniques, called dynamic force spectroscopy and unzipping force analysis of protein association, or UFAPA.

The process itself is much less overwhelming than the scientific terminology used to describe it.

An unzipping fork moves along a DNA molecule to separate the two strands of its double-helix structure as is necessary for retrieving its encoded information.

As it does so, it comes across those proteins attached to the DNA itself: exactly what Wang and Koch are interested in.

When the unzipping fork reaches these points, “a dramatic increase in the tension in the DNA, followed by a sudden tension reduction, is detected,” says the article.

Analysis of this can then reveal information about many factors involving DNA-protein interaction.

The result is the ability to distinguish “protein-DNA binding complexes on a site-specific, single-molecule basis,” the report says, meaning that it allows the proteins to be studied with great particularity.

Wang, a Cornell assistant professor of physics, had been working on the technique for almost three years, but says the research is only in the “laboratory-development stage” at this point.

She was assisted by Koch, a former physics graduate student who is now a researcher at Sandia National Laboratories, while performing the research.

The two biophysicists explained in their paper that the current methods for examining protein-DNA interactions were very limited in the factors of the relationship they were able to explore.

“The new single-molecule method provides specialized advantages and in some cases will enable measurements that thus far have been inaccessible,” the report claims.

This new technique opens many doors in the future of genetics research, Wang and Koch explained.

One application is its potential role in the current work towards understanding the genome.

“This could be used for restriction mapping, the first critical step in genomic sequencing, and for actual sequencing where the sequence of DNA is determined with a large number of restriction enzymes,” Wang told the Cornell Chronicle.

Wang also commented, “pharmaceutical companies could use UFAPA to screen libraries of small molecules for affinity to DNA.”

Other applications even include discovering and identifying new DNA binding proteins.

Archived article by Amy Green