Researchers are unlocking the secrets of Escherichia coli bacteria, or E. coli, thanks to long-term National Science Foundation support. There are more than 150 strains of the bacterium. One strain is an emerging cause of food-borne illness infecting 73,000 people every year, sometimes leading to kidney failure, and causing 60 deaths. Two leaders in E. coli research are here at Michigan.

Frederick C. Neidhardt, one of the nation’s premier researchers on E. coli, has had NSF support for his research for almost 47 continuous years. "From 1952-56, I was supported as a graduate student at Harvard on an NSF Predoctoral Fellowship," says Neidhardt, vice president emeritus for research and the F. G. Novy Distinguished University Professor Emeritus of Microbiology and Immunology. "And from 1958 onward, my research on the growth and regulation of metabolism of E. coli has been supported almost without interruption — at Harvard Medical School, Purdue University, and since 1970, the University of Michigan." Support continued right through last year when he closed his laboratory and retired from experimental laboratory work.

Over the years, Neidhardt and his research teams made at least two significant inroads in understanding this complicated bacterium. He developed a standardized cell system for growing and studying E. coli in a way that permits construction of databases of information on a single cell type, which included developing a now widely-used culture medium for bacterial growth studies. He also developed the first database on E. coli proteins.

Neidhardt’s final NSF grant supported an effort to "turn on" all of the genes of the E. coli genome in small orderly sets and then to identify their protein products–a feat that has never been accomplished for any cell. "We made good progress in developing methods and materials for turning on the genes, and for looking at the products, but the complete goal will be achieved only with improved and advanced methods by others in the near future," says Neidhardt.

"Put quite simply, the support from NSF has made my research possible,." he adds. "One cannot do experimental work in bacterial physiology and genetics without substantial financial support for equipment, supplies, travel to meetings, and personnel."

Rowena G. Matthews agrees. "The equipment we use was purchased with support from NSF, as were the very expensive supplies necessary for our experiments," she says. Matthews is the G. Robert Greenberg Distinguished University Professor of Biological Chemistry and the director of the Biophysics Research Division. She is also one of the world’s leading experts on folic acid, and a recipient of the prestigious National Institutes of Health Merit Award for long-term productivity in research. Matthews also received an NSF Predoctoral Fellowship when she began her graduate studies in 1963.

The NSF currently support Matthews’s study of a regulatory network of proteins in E. coli. In yet-unpublished work, Matthews and her collaborators have pioneered the use of a combination of mass spectrometry and the analysis of the proteome, the total protein output encoded by a genome. "Our work has focused on one regulatory protein, the leucine-responsive regulatory protein (Lrp), which regulates more than 50 genes in E. coli. We have been able to identify about ten additional genes whose expression is regulated by Lrp," says Matthews.

"NSF support has encouraged a rather unique industrial-academic collaboration between my laboratory, the laboratory of my co-principal investigator Robert Blumenthal from the Medical College of Ohio, and scientists at the Parke-Davis Research Division of Warner-Lambert Pharmaceuticals, especially Ruth VanBogelen," says Matthews. "NSF is very supportive of industrial-academic collaborations of this type and of the use of their funds for training of the next generation of researchers, which assures that such vital work will go on."