Our Science – Schneider Website

Thomas D. Schneider, Ph.D.

CCR Nanobiology Program Head, Molecular Information Theory Group Senior Investigator Building 469, Room 105 NCI-Frederick Frederick, MD 21702-1201 Phone:   301-846-5581 Fax:   301-846-5598 E-Mail:   toms@ncifcrf.gov Link: Other Homepage

Biography

After receiving a B.S. in biology at the Massachusetts Institute of Technology, Dr. Schneider obtained his Ph.D. in molecular biology with Larry Gold in the Department of Molecular, Cellular and Developmental Biology at the University of Colorado, Boulder. His thesis and postdoctoral work, also done at Boulder, were on the application of information theory to nucleic-acid binding sites. He was a member of the GenBank Advisory Committee. He helps to organize and run the international news group bionet.info-theory, which is devoted to the application of information theory to biology.

Research

Information Theory in Molecular Biology

Shannon's measure of information is useful for characterizing the DNA and RNA patterns that define genetic control systems. Dr. Schneider has shown that binding sites on nucleic acids usually contain just about the amount of information needed for molecules to find the sites in the genome. This is a working hypothesis, and exceptions can either destroy the hypothesis or reveal new phenomena. For this reason, he is studying several interesting anomalies.

The first major anomaly was found at bacteriophage T7 promoters. These sequences conserve twice as much information as the polymerase requires to locate them. The most likely explanation is that a second protein binds to the DNA. In another case, he discovered that the F incD region has a three-fold excess conservation, which implies that three proteins bind there. Both anomalies are being investigated experimentally. Thus, the project has three major components: theory, computer analysis, and molecular biology experiments. The theoretical work can be divided into several levels. Level 0 is the study of genetic sequences bound by proteins or other macromolecules, briefly described above. The success of this theory suggested that other work of Shannon should also apply to molecular biology. Level 1 theory introduces the more general concept of the molecular machine, and the concept of a machine capacity equivalent to Shannon's channel capacity. In Level 2, the Second Law of Thermodynamics is connected to the capacity theorem, and the limits on the functioning of Maxwell's Demon become clear. The practical application of this work for most molecular biologists will be the replacement of consensus sequences with better models. Consensus sequences are being used to characterize the binding sites of macromolecules on DNA and RNA. After aligning a set of binding-site sequences, the most frequent base is chosen. A position that contains 100 percent As will be represented by an A, while a position that is only 75 percent A will also be represented by an A. The consensus is frequently used to search for binding sites, and the number of mismatches to the consensus is counted. A mismatch to a 100 percent A position is much more severe than one to a 75 percent A, but this is not accounted for so the researcher is misled. Mathematically robust graphical replacements for the consensus sequences called the Sequence Logo and Sequence Walkers won't discard hard-earned data. The Walker, which is patented, has direct medical application because it can be used to distinguish polymorphisms from mutations in human sequences. The Walker method allows one to display many different binding sites simultaneously. This bird's-eye-view is a powerful tool for gene structure analysis. Further information and examples may be found on the Internet at the World Wide Web site:


http://www.ccrnp.ncifcrf.gov/~toms/

We collaborated on this research with Peter Rogan, Allegheny University of the Health Sciences.

Nanotechnology

Molecular information theory tells us how molecules function. The theory therefore tells us how to build useful devices at the molecular level. We have recently begun several new projects in nanotechnology. Nanoprobes are single-molecule detectors while the Medusa(TM) sequencer is a single-molecule DNA sequencing device. See my home page for more details on all projects.

This page was last updated on 6/12/2008.