Professor of Mathematical Sciences
Rensselaer Polytechnic Institute

Education:
Ph.D., Mathematics, Massachusetts Institute of Technology, 1974
B.Sc., Mathematics, First Class Honours , McGill University, 1970

Career Highlights:
After completing his doctorate degree in mathematics, Zuker spent 20 years as a research officer at the Institute for Biological Sciences at the National Research Council of Canada in Ottawa. During his tenure there, he spent the 1991-'92 academic year on sabbatical as a visiting scholar in the mathematics department at Stanford University. Two years later, Zuker accepted a position as an associate professor of biomedical computing at what is now the Center for Computational Biology at Washington University School of Medicine in St. Louis. He joined Rensselaer in 2000 and holds the rank of professor.

Zuker has given over 100 invited and plenary lectures throughout the world in such countries as Sweden , Poland, Israel, and Japan. Some of his other professional activities include serving as a committee and panel member for the National Institutes of Health, National Cancer Institute, and the Medical Research Council of Canada. He has served as an editorial board member of GENE-COMBIS, Computer Applications in the Biological Sciences, and the Bulletin of Mathematical Biology. From 1989-’94, Zuker was a Fellow of the Evolutionary Biology Program of the Canadian Institute for Advanced Research (CIAR).

Research Areas:
The central theme in Zuker's research has been the development of algorithms to predict RNA and DNA secondary structure by free energy minimization using empirically derived thermodynamic parameters. Modeling and algorithm development have been closely coupled with the derivation of “nearest neighbor” and other energy rules from the laboratories of Zuker’s colleagues D.H. Turner, University of Rochester and J. SantaLucia Jr., Wayne State University. The algorithms allow the use of several types of constraints that can incorporate experimental information on the existence or non-existence of specific base pairs.

The algorithms’ many applications include the abilities to make predictions of RNA secondary structures, with or without constraints, and to produce a reasonably small number of secondary structures that can be experimentally tested for validity. The tools also can create secondary structure predictions for single RNA viruses. Other applications of Zuker’s algorithms include RNA folding software that has been useful in designing anti-sense nucleic acids or even ribozymes that can be used to target an mRNA and DNA secondary structure predictions. This software has proven useful in the design of probes, polymerase chain reaction (PCR) primers, and molecular beacons.

More recently, Zuker's group has derived RNA nearest neighbor rules by analyzing base pair stacking frequencies in a large database of known secondary structures. His current work is focused on the computation of partition functions for systems containing two molecules that can fold as well as hybridize with each other. This work allows researchers to predict optical density and heat capacity melting curves, and is a profound improvement over minimum energy foldings of single sequences. He also is developing a fast search algorithm based on hashing to find likely targets of a DNA “query” sequence in genomic DNA. Scoring is of a DNA or RNA query in genomic DNA or mRNA sequence databases.

Selected Publications:
M. Zuker, “On Finding All Suboptimal Foldings of an RNA Molecule,” Science, 244, 48-52, (1989).

M. Zuker and A.B. Jacobson, “Using Reliability Information to Annotate RNA Secondary Structures,” RNA, 4, (6), 669-679, (1998).

D.H. Mathews, J. Sabina, M. Zuker, and D.H. Turner, “Expanded Sequence Dependence of Thermodynamic Parameters Improves Prediction of RNA Secondary Structure,” Journal of Molecular Biology, 288, (5), 911-940, (1999).

R.B. Lyngsø, M. Zuker, and C.N.S. Pedersen, “Fast Evaluation of Internal Loops in RNA Secondary Structure Prediction,” Bioinformatics, 15, (6), 440-445, (1999).

M. Zuker, “Calculating Nucleic Acid Secondary Structure,” Current Opinion in Structural Biology, 10, (3), 303-310, (2000).

J.-M. Rouillard, C.J. Herbert ,and M. Zuker, “OligoArray: Genome-Scale Oligonucleotide Design for Microarrays,” Bioinformatics, 18, (3), 486-487, (2002).

M. Zuker, “Mfold Web Server for Nucleic Acid Folding and Hybridization Prediction,” Nucleic Acids Research, 31, (13), 3406-3415, (2003).

J.-M. Rouillard, M. Zuker, and E. Gulari, “OligoArray 2.0: Design of Oligonucleotide Probes for DNA Microarrays Using a Thermodynamic Approach,” Nucleic Acids Research, 31, (12), 3057-3062, (2003).

D.H. Mathews and M. Zuker, “Predictive Methods Using RNA Sequences,” in Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, A. Baxevanis and F. Ouellette, eds., third edition, John Wiley & Sons, New York, Chapter 7, (2003).

R.A. Dimitrov and M. Zuker, “Prediction of Hybridization and Melting for Double-Stranded Nucleic Acids,” Biophysical Journal, in press.

Contact Information:
Michael Zuker
(518) 276-6902
zukerm@rpi.edu
http://www.rpi.edu/~zukerm/