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Cathy Squires - Career Profile

It All Started With Chicken Water

squiresCathy Squires got her first experience with microbes growing up on her family’s farm in Sacramento, Calif. She started her college education thinking she’d one day be a medical lab technician. Since then, Dr. Squires has earned a Ph.D. and built a career as a research scientist studying the means by which bacteria churn out copies of their DNA and manage their reproduction. She’s now a professor of microbiology at Tufts University School of Medicine in Boston, Mass. This is her story of how she got into a career in microbiology.

"Our high school sophomore biology teacher asked the class to bring in a water sample from home to examine under the microscope. He suggested we take water from where the cows, chickens, or pets drank, so my father’s chicken water was a natural source for me to sample. One look at my chicken water under the microscope and the normally reserved biology teacher became completely excited; the sample was loaded with microbes! Amoebae, paramecia, algae—many busy, motile bacteria and oddly shaped characters floated by our eyes. The whole class was delighted, and I was charged with bringing in a sample of that chicken water for every biology class the rest of the time I was in high school. The excitement of this first exposure to microbiology has always stayed with me.

From the time I was eight years old, it had been taken for granted in my family that after high school I would enroll in the University of California, Davis, but my future as a bacteriologist was still far from anyone’s mind. UC Davis was primarily an agricultural school at that time, but it also had a school of veterinary medicine and ran its own creamery. My uncle had a dairy close to UC Davis and sold his milk to the creamery. The UC Davis veterinarians and their students who came to treat my uncle’s sick cows fascinated my cousins and me. I knew about many microbial diseases long before I knew about microbes; outbreaks of mastitis, anthrax, pink eye, brucellosis, and so on were fairly common occurrences on the farm. I was very impressed by the fact that when a cow died of anthrax, my uncle had to burn her on the spot and flame the surrounding grass as well.

The closest profession to microbiology that my high school career counselor, a nurse, could recommend was being a medical laboratory technician. With this goal in mind, I asked, on acceptance at UC Davis, to be put into the suggested training program as a biochemistry major. In fact, UC Davis had no undergraduate biochemistry major, so I was assigned to bacteriology instead. This turned out to be a wonderful and fortuitous match, despite the apparently arbitrary way the decision was made. The Bacteriology Department at UC Davis at that time had a truly remarkable and renowned faculty [including] Mortimer P. Starr, an internationally renowned expert in microbial taxonomy. Starr’s classes were adventures in sampling—from vinegar factories and brewing houses to salt ponds and San Francisco Bay mud. I specialized in cow pies from my uncle’s dairy and purified what was then the largest known bacterium, Caryophanon.

Monty Reynolds taught the introductory microbiology course and was one of the most memorable professors I have ever had. An extremely hyperkinetic type, he literally jumped around the lectern. He also showed a lot of unforgettable movies, many obtained from Army archives. We saw the consequences of a rabid wolf biting villagers in a remote area of Iran and a film of a UC Berkeley student who had accidentally pricked himself with a rose thorn and become infected with tetanus (the student allowed the course of his infection and recovery to be filmed). The images are still vivid in my mind’s eye.

My introduction to microbiological research began in the summer between my junior and senior years. I was the lucky recipient of a National Science Foundation undergraduate research fellowship and was picked to work in John Ingraham’s laboratory. He put me to work studying the phenomenon of cold shock—what goes on when bacterial cells are subjected to a sudden large drop in growth temperature. I was fascinated by the topic and continued to pursue it until graduation.

By this time, I was hooked on research and a bit confused about the medical lab tech option. Dr. Ingraham rescued me by offering a research technician’s job in his lab. I was delighted to accept. My role was to try out Ingraham’s novel and exciting ideas. If they worked, the project was given to a graduate student or postdoctoral fellow; if not, the idea was dropped. I quickly learned that I didn’t have enough information to be a major contributor to the new ideas. It was clear that I needed more class work and training—my motivation for pursuing a master’s degree in microbiology at UC Davis.

During this period, I married Craig Squires, another technician in the Bacteriology Department. Craig was anxious to move to UC Santa Barbara and work for Ellis Englesberg, studying a novel positive regulatory system—the arabinose operon. The UCSB Biology Department welcomed us and gave me several options: work as a technician, run the microbiology teaching labs, or become a Ph.D. student. By that time, I was totally hooked on research but still thought I didn’t know enough to be an insightful and independent researcher, so I opted for the doctoral program. Again, I was fortunate to receive superb training. My degree in biochemistry and molecular biology was completed under the supervision of an outstanding mentor, Nancy Lee. I have always tried to emulate her wonderfully rigorous and thoughtful approach to science. By the time I received my degree, I was confident that I could purify and analyze virtually any protein.

For postdoctoral training I wanted to work on one of the major regulatory puzzles of the time: how amino acid biosynthetic operons are regulated. I knew that to stay in research and be successful, I would need the same kind of mentoring, confidence in my abilities, and networking help I had received from John Ingraham, Nancy Lee, and many of the other faculty at UC Davis and UC Santa Barbara. Somehow I knew enough to seek out Charles Yanofsky at Stanford University and ask to work on the tryptophan operon. Yanofsky took on Craig as a research associate as well, and this time was the beginning of an exciting period during which the group collectively discovered the novel regulatory phenomenon of transcription attenuation.

Again, I was very fortunate to have a superb mentor. When the time came for me to leave Stanford, I agonized over what my independent research project should be when I took my first faculty position. After several months, I settled on the mysterious regulation of ribosome biosynthesis. Building on the success of Naomi Franklin in making fusions between phage promoters and tryptophan biosynthetic genes, I decided that the gene fusion approach would provide a unique handle on studying ribosomal gene expression. The only problem was that I wasn’t yet schooled in the newly created recombinant DNA technology. Yanofsky allowed me to spend the last four months of my postdoctoral training period in Herb Boyer’s lab at UC San Francisco. There, Boyer and Pat Green taught me how to do endonuclease restriction digests, ligations, and transformations and to run agarose gels; in short, they taught me the fundamentals of the emerging recombinant DNA technology.

I have worked on the regulation of ribosomal RNA (rRNA) synthesis ever since that time and feel very fortunate to have had excellent students, postdoctoral fellows, and associates to share this project. We have applied genetics, biochemistry, molecular biology, and physiology—the patchwork of my training and interests—to our studies of ribosome synthesis. We have studied transcription regulation, using gene fusions to characterize a special feature of rRNA synthesis—transcription anti-termination. We have also studied cell physiology and genetics as they relate to copies of ribosomal genes. We were successful in constructing a strain of Escherichia coli with no intact chromosomal rRNA operons. The cell’s only source of ribosomal genes is a plasmid. By exchanging E. coli sequences on the plasmid with those of other microbes, we are able to manipulate a cell’s ribosome content in many unexpected ways and thereby pose novel questions about the cell’s translation machinery.

I remain as enthusiastic and excited about microbiological research today as when I started more than 30 years ago. My advice to students and new researchers is always to try to pursue what really interests and excites you; there is no substitute for enthusiasm in research."

(This profile was excerpted from a book called Many Faces, Many Microbes, a collection of personal essays written by a wide variety of microbiologists.)

 

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