Note: Because some of the information in this article may be outdated, it has been archived.
Will molecular rulers measure nano-scale structures such as those found in DNA?
A ruler is generally used to measure the length of an object. A protractor or compass can be used to measure distance along a two dimensional curve but it is laborious. Is it possible to design a molecular ruler that can measure local bends in DNA? If so, such a ruler would be a priceless tool in several ways:
- to unravel changes in structural characteristics of macromolecules bound by proteins.
- to assist in DNA transcription regulation, recombinations, and packaging into nucleosomes.
- to provide clues to the origin of DNA replication and the recombination process.
Designing the method
Is is possible to separate different-size molecules?
To manufacture a molecular ruler, the first step is to design an experiment that will separate nucleic acid fragments according to size. How could molecules be separated by size? There are a few options:
Imagine a beaker filled with long, wiry charged molecules. Optical tweezers mimicking handheld tweezers can extract the molecules one at a time. This procedure, however, is impractical. It would take a long time to sort through even one cubic centimeter of the beaker’s contents.
Genome-sequencing robotics is another option. This process sends molecules and buffers through capillaries filled with polymers. The robots are linked to computers, which analyze the data. However, the cost of the robots and the computers, as well as the need for a laboratory specially-designed for the task, makes this procedure not easily accessible to all scientists.
Inexpensive gel can be used to design a molecular ruler.
- The easiest method, called gel electrophoresis, uses ordinary components similar to Jell-O to separate the molecules. To make the gel, a specific quantity of gelatin is poured into an appropriate volume of boiling water until it dissolves. Once cooled, the gel forms matrices, which have pores through which molecules can pass. The matrices needed to separate nucleic acids are usually made from polymers such as agarose or polyacrylamide.
Cooking Up a Molecular Ruler
Scientists create molecular ruler
2001-02-14 News article, “Scientists Create Molecular Rulers Enabling Precise Construction of Nanoscale Structures,” about a breakthrough in the development of a molecular ruler, enabling the construction of nanoscale structures.
Picture gallery of DNA
In this gallery, images show the kinks, or bends, in DNA.
Steven Chu bio
This Nobel laureate inspired the author to pursue research on the molecular ruler.
The Crothers lab
This lab made breakthroughs in the design of molecular rulers.
Call for math and science partnerships
The National Science Foundation is seeking government funding for states and local school districts to work with mathematicians, scientists, and engineers of higher education in order to help raise math and science standards and provide math and science training for teachers in K-12 education. The NSF is requesting comments on this initiative. Read their statement and, if you agree, also write a letter to your congressman in support.
For teachers: biochemistry resources
Project Galileo offers ready-to-use materials to teachers of chemistry and biochemistry. Registration and login are required.
Genomics Analogy Model for Educators (GAME)
The GAME website is a tool for high school science teachers and higher education instructors who teach genomics but who do not have a molecular biology background. Useful analogies and resources are available for teachers to use in their classroom.
Biointeractive is a website and a collection of biology-focused teaching materials created by the Howard Hughes Medical Institute. Many materials are available to educators for free and can be ordered from the catalog. The site’s information and links are also useful to high school seniors and college-level students.
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- »Kerppola, T. K. Proc. Nat. Acad. USA 1996, 93:10117-10122.
- »Drak, J., Crothers, D. M. Proc. Nat. Acad. 1991, USA 88:3074-3078.
- »Perkins, T.T., Smith, D.E., Chu, S. Science 1994, 264:819-822.