Chemotaxis in E. coli

My very favorite discovery was discovering that in bacterial cells, which do something called chemotaxis, they move towards something that they like and they move away from something they don't like. And we discovered that the set of proteins that allow you to do chemotaxis are localized at the pole of the cell. And nobody wanted to believe that. And we actually, not only did we prove it in Caulobacter, but to get the world to believe us, we did it in E. coli where everyone was working. And we published in one issue of Science, two papers. The lead article was E. coli. The report in the back was Caulobacter. But in each one, and these papers were mostly controls to show that in fact, the chemo receptors to work appropriately had to be localized, and the cell knew how to put it there. These were my favorite experiments. Janine Maddock was a postdoc in the lab and her work was simply brilliant.

CtrA Transcription Factor

There was another discovery that was, that came earlier that was also one of my favorite and seminal, and that was the discovery of a transcription factor. Transcription factor, dime a dozen. But this one, CtrA, was found by one of my graduate students who said, why don't I isolate mutants of this thing and let's just take Caulobacter and get mutants that can't swim, can't make a flagellum. And he did, but then he found that it was lethal. I said, you can live without a flagellum. Why is it lethal? To make a very long story short, the mutation was in this transcription factor that controlled not only flagellum biogenesis, not only pili biogenesis, but controlled when DNA replication happened, controlled cell division genes, controlled a huge number of critical events that had to occur at specific times in the cell cycle. And what was so exciting was that I had groups in my lab studying all these different phenomena, and it turned out that they all use the CtrA transcription factor. They all had the same promoter in front of the critical region. And that was the start of completing the genetic circuitry that controlled the progression of the cell cycle. All the work with CtrA was published in Cell.

Lucy Shapiro (b. 1940, New York City) is a developmental biologist and Professor Emeritus of Developmental Biology at Stanford University where she has been a faculty member since 1989. She held the Virginia and D.K. Ludwig Chair in Cancer Research and served as director of the Beckman Center for Molecular and Genetic Medicine. Dr. Shapiro’s lab has focused on studying Caulobacter crescentus, one of the simplest organisms that divides asymmetrically into different cell types, to uncover fundamental principles of developmental biology.

Dr. Shapiro received her Bachelor of Arts in Biology and Fine Arts from Brooklyn College in 1962, and her Ph.D. In Molecular Biology from Albert Einstein College of Medicine in 1966. In 1986, Shapiro moved to the Columbia University School of Medicine as the first female chair of the Department of Microbiology and Immunology. Two years later, in 1989, Shapiro moved to Stanford University and founded the Department of Developmental Biology.

In the early 1990s, Dr. Shapiro became involved in policy work. She was invited to the White House to speak to President Bill Clinton and his Cabinet about the potential threats to the public posed by the increase in antibiotic resistance, emerging infectious diseases, and the possibility of bioterrorism. She then went on to serve as a scientific advisor to the Clinton administration and advisor on bioterrorism to the secretary of homeland security, Tom Ridge, and to the secretary of state, Condoleezza Rice during the George W. Bush administration.

In addition to her research, Dr. Shapiro co-founded the anti-infectives discovery company Anacor Pharmaceuticals to develop new types of antibiotics and antifungals. This has resulted in the production of two FDA approved drugs; Kerydin, a treatment for toenail fungus and Crisaborole, to treat atopic dermatitis. Anacor Pharmaceuticals was acquired by Pfizer in May 2016. She also co-founded Boragen, an agricultural innovation company that merged with AgriMetis to form 5Metis, Inc, where she serves on the board. She also serves on the board of directors at GlaxoSmithKline and Pacific BioSciences, Inc.

Dr. Shapiro has received numerous awards including the National Medal of Science awarded by President Barack Obama, the Linus Pauling Medal, Dickson Prize in Science, Canada Gairdner International Award, Federation of American Societies for Experimental Biology (FASEB) Excellence in Science Award, the Selman Waksman Award, the Louisa Gross Horwitz Prize, the Abbott Lifetime Achievement Award, the John Scott Award, and the Pearl Meister Greengard Prize.