By Dale Noel, Ph.D.
Starting their marriage as poor farmers in the Arkansas Ozarks, my parents aspired to be teachers and put each other through college as they raised a family. My father graduated when I began sixth grade, and my mother graduated the same month I graduated from high school. Thereafter they were educators in the public schools of St. Charles, Missouri. I deeply respected their devotion to their students, their craft, and the cause of public education, but I didn’t see in myself the other qualities that made them good teachers. Instead, what I knew was that in some manner I would be a scientist.
In college, I became fascinated by a very basic unsolved problem, how water-soluble molecules and ions cross membranes in a selective fashion. For my PhD dissertation at UC-Berkeley, I studied a high-affinity transport system in bacteria under the direction of Giovanna Ferro-Luzzi Ames. Her life work provided the basic understanding of the very important class of proteins known as ABC transporters. I was happy to be part of the ground-breaking studies she was doing at the time, but they were not at a stage to provide the type of enlightenment about transport that I sought. Nevertheless, by introducing me to the world of bacterial genetics and the power of combining genetics and biochemistry, she strongly influenced my future approach to biology and biochemistry.
Graduate school also influenced my later decisions about teaching. First, I had a very
positive experience as a TA. Perhaps I could fit into classroom teaching and learning. Second, my research and an audited course in photosynthesis fueled an intense interest in all of membrane bioenergetics, which I poured into a graduate course I taught for several years after joining the faculty at Marquette. Soon after I began teaching that course, structures for bacterial type 2 reaction centers and a bit later the bacterial bc1 complex were published, beautifully culminating the findings of years of research on these two passions of mine. Graduate and undergraduate students in all of my lecture courses thenceforth had to suffer my fascination with these biological machines. By that time, though, I was happily pursuing another problem in my own research.
After grad school, I turned to the study of symbiotic nitrogen fixation. The questions were how root nodules developed on leguminous plants and how the bacteria infected the nodules. This quest took me through two postdoctoral research stints and most of my years at Marquette. The first postdoc was with Winston Brill at UW-Madison. In Madison, I also met my future wife, Diane. In my research, I began isolating bacterial mutants to let them tell me what was important for symbiosis. However, what gave me the most citations was dabbling in a field I knew nothing about, the ecology of soil bacteria. I developed a technique that revealed the surprising diversity, abundance, and population changes of symbiotic bacteria present in the soil of a field that had not seen the host plant for decades. It explained the basis of what is known as the competition problem of legume inoculants.
Noel Lab members and families in June 1990
After this postdoc, I accepted a two-year position in Mexico. A large group of very talented students and scientists had been assembled to found an institute whose mission was to study nitrogen fixation, but none of them had ever studied it. In essence, I was to teach them the details of studying nitrogen fixation and the symbiosis. I saw the institute develop from a pile of bricks on a craggy mountainside to the largest center in the world studying the symbiosis. There I began studying the particular symbiotic partners that I still study. For reasons of national interest, they studied bean as the host. I was delighted to make this switch, because the bacterial partner was very easy to study genetically, compared with the slow-growing partner of soybean that I had studied in Brill’s lab.
I started at Marquette in August of 1983. My students began to study the bacterial mutants I had isolated in Mexico. Geneticists studying the symbiosis had shown that bacterial plasmids were very important. Some of my mutants showed that the bacterial chromosome also carried important determinants, but there was a theme to most of the chromosomal mutants: they elicited nodules but were deficient in nodule development. We soon realized they were specifically blocked in infection. Other geneticists had overlooked this phenotype because, surprisingly, they didn’t bother to observe nodules closely as they developed. My goal for us was to explain the biochemical basis of the infection defects. It turned out that we were able to do that in relatively short order. In the following I am highlighting contributions of graduate students. I regret that I only have space to mention the first and last of the 87 undergraduates who have worked in my lab. My greatest joy has been working with these many undergraduates, as well as the graduate students, in individual projects. I’m also grateful to research technicians – Deb Turowski, Bruce Schultz, and Jodie Box – for their dedication and key insights.
|The Noel Lab in 1992|
Bruce Kulpaca (B.S. ‘85), an undergraduate, and I discovered that a large class of these infection mutants were defective in forming the lawn of O-antigen polysaccharides that project from outer membrane of the bacteria. Thereafter, much of the work in the lab was devoted to studying this complex polysaccharide. We began a collaboration spanning two decades with Russ Carlson at the University of Georgia to determine its structure and the truncated structures of various mutants. Joe Cava (B.S.’82, Ph.D.’88) cloned the genes, generated site-directed mutations and developed a physical map of each of the three genomic regions that direct the synthesis of the O-antigen. Benita Brink (Ph.D. ’89) expanded the story to other rhizobial species and generated a chromosomal linkage map as well. Linda Eisenschenk's (M.S. ’93) work suggested that one reason the O-antigen is required is that it protects against hydrophobic plant toxins. Another aspect of its function seems to involve environmentally-induced structural changes discovered by Hong Tao (M.S. ’91). Dom Duelli (Ph.D. ’99) then identified plant compounds that induce these changes and how the O-antigen structure changes upon induction. More recently, we have studied how this complicated molecule is synthesized. The matching of individual genes with the orders and specific linkages of the sugars was discovered by Kristylea Ojeda (B.S. ’03, Ph.D. ’09). Current graduate student Tiezheng Li is studying the enzymology of the first steps of the synthesis; his results indicate a surprising difference to the generalized notion of how polysaccharide synthesis operates. All of this work has made the O-antigen of our bacterium a premier model for understanding the genetics, synthesis, and roles of this type of molecule.
Noel Lab members and alumni at Christmas 2006
Study of another large class of the symbiotic mutants got off to a shaky start because of bad microbiology on my part. They turned out to be purine auxotrophs but gave colonies on our minimal-medium plates because they are terrific scavengers of the small amount of purine in the agar, yielding low numbers of cells that produce copious exopolysaccharide such that the colonies do not look much smaller than normal. Unraveling this led us to two fascinating stories. The late Ron Diebold (Ph.D. ’88) studied the exopolysaccharides and proposed that only one of two types of nodule development requires the production of these secreted molecules. This generalization still holds. He also made observations that caused us to look closely at a purine intermediate known as AICAR. Jeff Newman (Ph.D. ’92) followed Ron's initial observations with very thorough and creative studies that convinced the field that AICAR coming from the bacteria plays a special role in infection.
Noel Lab members at a backyard cookout in 2011
The next graduate student, Olivia Jahn (Ph.D. ’98), discovered a very abundant symbiosis-specific protein she named BacS. In the first reverse genetics project in the lab, she could find no requirement for this protein. A decade later its abundance was explained when two undergraduates, Laura Muck (summer research student ’11) and Sihui Yang (B.S. ’13), showed that it is a phasin protein necessary for production of the bacterial plastic known as polyhydroxybutyrate. Zac Lunak, my last grad student, is asking why bacteria have different types of terminal oxidases and getting a novel answer with our symbiotic bacterium, Rhizobium etli. This project is bringing me full circle back to my interests as a student.
I have been the instructor for three courses for undergraduates. The first was Experimental Genetics. I then taught Microbiology, my favorite course, for several years. Because there was no microbiology lab course during part of these years, I developed lab exercises in place of the normal discussion sections, which the students and I greatly enjoyed. Then, for about a decade I taught the second semester of introductory biology. I have alluded to the graduate course I taught for many years and more lately I have taught bacterial physiology and genetics, because some of our students have a special need to learn the basics of these subjects. I may not have the skill or personality of my parents or many of the great teachers in this department, but I do passionately want students to learn. I believe the most important skill for learning is to ask thoughtful questions, and I firmly support the philosophy of our department, that biology is best learned by exploring it with your hands as well as your mind.