04/08/19 - 4:00 PM to 5:00 PM
Kolthoff Lectureship #1: Professor Suzanne Walker
Izaak M. Kolthoff Lectureship in Chemistry
Pathway-directed screening for antibacterial compounds
High throughput screening has become an important component of research in chemical biology and drug discovery. Screening strategies classically fall into two categories: target-based screens and phenotypic screens. Target-based screens involve cell-free biochemical assays of a chosen target where the goal is to identify activity modulators (e.g., inhibitors of that target). Phenotypic screens are “unbiased” in the sense that there is no predetermined target; the goal is to identify a compound that affects a phenotype (e.g., a compound that inhibits bacterial growth). For the last 15 to 20 years there has been a spirited dialogue about the advantages and disadvantages of these dichotomous screening approaches, but pretty much everyone agrees that a huge amount of time is wasted with both strategies following up on junk compounds. In this lecture, I am going to talk about how my lab approaches high throughput screening for the discovery of compounds that hit antimicrobial targets. I will show that it is possible – using pathway-specific and pathway-directed cell-based screens – to immediately identify bioactive compounds that inhibit pathways in a specified area of biological space. I will talk about examples of inhibitors we have identified that target essential and non-essential (but important) proteins in the S. aureus cell envelope.
Monday, April 8
Conference Rooms ABC, 4th floor, Coffman Memorial Union
Suzanne Walker received a Bachelor of Arts in English literature at the University of Chicago and a doctorate in organic chemistry at Princeton University. She joined the faculty at Princeton as an instructor of chemistry in 1995 and was promoted to associate professor with tenure in 2001. Shortly thereafter (2003), she became the first woman to attain the rank of full professor of chemistry at Princeton. In 2004, she left Princeton to join the faculty at the Harvard Medical School. She helped build the Harvard University doctorate program in chemical biology, which was established in 2005, and has served as director of the program since 2011. She also serves as an associate editor for the Journal of the American Chemical Society, handing papers in the areas of chemical biology and biochemistry.
Professor Walker is known for contributions in two major areas. One is the bacterial cell envelope. The Walker lab has developed methods to study the biosynthesis of peptidoglycan and other cell envelope pathways, and has developed novel approaches to discover and characterize new antibacterial targets and compounds. She has also made fundamental contributions to understanding O-GlcNAc transferase (OGT), an unusual glycosyltransferase that is essential for mammalian cell survival. Her laboratory has carried out the foundational biochemistry on OGT (mechanism and structure) and is developing methods to link in vitro mechanism with cellular function.
Walker has been recognized for her work through a number of awards, including a Camille Dreyfus Teacher-Scholar Award, an Alfred P. Sloan Foundation Fellowship, the Emil Thomas Kaiser Award in Protein Chemistry, an Arthur C. Cope Scholar Award, and most recently, election to the American Academy of Microbiology (2019). She has also been honored to be a W.S. Johnson Symposium speaker (Stanford 2011 ), the Ada Doisy Lecturer in Biochemistry (University of Illinois 2015), the Mary Sue Coleman Lecturer in the Life Sciences (University of Michigan 2015), a Frontiers in Chemistry Distinguished Lecturer (Scripps 2016), the T.Y. Shen Distinguished Lecturer in Biological Chemistry (MIT, 2016), the National Institutes of Health Director’s WALS Lecturer (Bethesda 2017), the Andrew Braisted Award Lecturer in Chemical Biology (Berkeley-UCSF 2017), and the Irwin Goldstein Lecturer in Glycobiology (University of Michigan 2019). She is especially pleased to honor the legacy of I.M. Kolthoff with a series of lectures at the University of Minnesota!
Kolthoff Lectureship in Chemistry
Izaak Maurits Kolthoff was born on February 11, 1894, in Almelo, Holland. He died on March 4, 1993, in St. Paul, Minnesota. In 1911, he entered the University of Utrecht, Holland. He published his first paper on acid titrations in 1915. On the basis of his world-renowned reputation, he was invited to join the faculty of the University of Minnesota’s Department of Chemistry in 1927. By the time of his retirement from the University in 1962, he had published approximately 800 papers. He continued to publish approximately 150 more papers until his health failed. His research, covering approximately a dozen areas of chemistry, was recognized by many medals and memberships in learned societies throughout the world, including the National Academy of Sciences and the Nichols Medal of the American Chemical Society. Best known to the general public is his work on synthetic rubber. During World War II, the government established a comprehensive research program at major industrial companies and several universities, including Minnesota. Kolthoff quickly assembled a large research group and made major contributions to the program. Many of Kolthoff’s graduate students went on to successful careers in industry and academic life and, in turn, trained many more. In 1982, it was estimated that approximately 1,100 Ph.D. holders could trace their scientific roots to Kolthoff. When the Analytical Division of the American Chemical Society inaugurated the Giddings Award for Excellence in Education in 1983, he was the first recipient.