Michael James is an outstanding scientist who is happiest and at his best in the lab with his students and postdocs." That comment, which comes from William Bridger, chair of the Department of Biochemistry at the University, was made in support of the University's recent elevation of James, a professor of biochemistry, to the prestigious appointment of "university professor."
James concedes the preference for the laboratory. The scientist whom Bridger describes as "one of the real stars of the University of Alberta" points to a desk that seems ready to buckle under haphazard layers of books and papers and reveals that he is not, never has been, and never will be a candidate for an administrator-of-the-month award.
James has a preoccupation with order, but that (obviously) has nothing to do with the top of his desk. What preoccupies him is the orderly arrangement of atoms within enzymes and proteins. A pioneer in the field of protein crystallography, James established the first Canadian laboratory devoted to that pursuit (at the U of A in 1968). Since that time he and his students have described the threedimensional structures of many enzymes and other proteins that are of profound scientific interest and may lay the framework for new classes of therapeutic agents.
The work of the new university professor has not gone unacknowledged. In 1988, James received a University of Alberta Research Prize (now known as the Kaplan Prize) and the following year he was elected into fellowship in the Royal Society of London — only the third U of A faculty member to be so honored, and the first from the Faculty of Medicine. Last year the Canadian Federation of Biological Societies presented him its G. Malcolm Brown Prize, an honor dispensed only once every three years.
The awards recognize James's meticulous and inspired work in employing the techniques of x-ray crystallography to map the chemical structure of proteins. (X-ray crystallography provides information I about the three-dimensional arrangements of the atoms in a molecule through I the diffraction patterns formed by x-rays , passed through a crystal of the molecule.)
In 1989 James led a U of A team that received world-wide attention when it determined the structure of renin, an enzyme that plays a key role in the early development of high blood pressure. This discovery is regarded as being a major step which takes scientists closer to the development of drugs which treat hypertension bv inhibiting the action of renin.
"The things we are doing now are openended," said James in an interview this spring, shortly after he received word of I his appointment as a university professor. (The appointment took effect on 1 July 1993.)
One project that's high on his agenda concerns an enzyme that is produced by bacteria and nullifies the antibiotic effects I of penicillin. James describes this enzvme, which has the name beta-lactamase, as a missile that the bacteria makes to shoot down the penicillin. What's needed, he says, is an "anti-missile missile" — an inhibitor that will block out the resistance factor so that penicillin can be used once again to destroy the bacteria.
James points out that when penicillin was introduced in the early 1950s a certain few bacteria - but onlv a few - continued to grow even in high concentrations of the drug. Today, he estimates, if a great many bacteria were isolated, 90 per cent would prove to be immune to the effects of penicillin.
James's lab has already determined the structure of the beta-lactamase that makes the E. coli bacteria penicillin-resistant (the work was done by Natalie Strynadka,'83 BSc, '90 PhD, a J. Gordin Kaplan postdoctoral fellow), and investigations are now taking place using a mutant form of beta-lactamase which breaks a bond in the penicillin molecule while remaining stuck fast to it. The molecular complex formed by the fixing of the beta-lactamase to the penicillin is now being crystallized and its stucture studied.
"We now want to use this information to try and design inhibitors that will block out the resistance factor that destroys this class of antibiotics, so that penicillin can be used once again to destroy the bacteria," says James.
The respected protein crystallographer first became intrigued by the possibilities of using crystallography to determine a molecule's appearance while an undergraduate chemistry student at the University versity of Manitoba, and he did his master's degree there in the geology department — at that time the only department offering graduate instruction in crystallography at that institution.
James became familiar with the structure of penicillin while a student at Oxford University in the early 1960s. There he worked on the structure of a semisynthetic penicillin molecule in the lab of Dorothy Hodgkin and was a member of her group when she won the 1964 Nobel Prize in Chemistry.
A native of Vancouver, James came to the U of A in 1967 to work as a postdoctoral fellow in the Department of Chemistry, where he did x-ray crystallography with David Hall and Raymond Lemieux. In 1974, having by this time moved to the Department of Biochemistry, he was part of the Group in Protein Structure and Function established at the U of A by the Medical Research Council. That same year, he accomplished the first protein structure determination in Canada.
Three years later, his group gained international attention when it was the first in the world to obtain the structure of the enzyme penicillopepsin. Another important breakthrough from his lab was the determination of the structure of troponin C, a protein that is an important regulatory component of muscle.
James says that the work done in his lab is not necessarily directed towards a particular disease. "We're working on a series of biochemical systems and ultimately each of these small projects will be important in understanding the over-all story."
And, he says, noting the increased emphasis being given to clinical work, "What we're doing may not have direct clinical application but as we understand the fundamental chemical function of molecules, this knowledge will apply to the health care field."
Published Autumn 1993.