Kolthoff Lectureship #1: Professor Suzanne Walker, Pathway-directed screening for antibacterial compounds

Lecture, 4 p.m. Monday, April 8, Room 331, Smith Hall.

A reception follows (all are welcome) from 5 to 6:30 p.m. Monday, April 8, Conference Rooms ABC, 4th floor, Coffman Memorial Union

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.

Professor Walker

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.